DOCSLIB.ORG

Is Intestinal Metaplasia of the Stomach Reversible? Gut: First Published As 10.1136/Gut.52.1.1 on 1 January 2003

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Is Intestinal Metaplasia of the Stomach Reversible? Gut: First Published As 10.1136/Gut.52.1.1 on 1 January 2003 1 LEADING ARTICLE Is intestinal metaplasia of the stomach reversible? Gut: first published as 10.1136/gut.52.1.1 on 1 January 2003. Downloaded from M M Walker ............................................................................................................................. Gut 2003;52:1–4 Intestinal metaplasia (IM) of the stomach is a risk factor another, which implies adaptation to environ- in developing intestinal-type gastric cancer and hence mental stimuli, and that embryological commit- ments can be reversed or erased under certain the question of reversibility is vital. There is emerging circumstances.1 Epidemiological studies have epidemiological evidence that with long term follow up, shown that IM in the stomach has a high cancer IM may be reversible although a combination of risk and is therefore defined as a precancerous condition—a clinical state associated with a antioxidant agents and eradication of H pylori may be significantly increased risk of cancer. Dysplasia is necessary to achieve this. The pathogenesis of IM is a precancerous lesion—a histopathological ab- currently being elucidated and it is likely that a normality in which cancer is more likely to occur than in its apparently normal counterpart.2 For combination of bacterial, host, and environmental example, a study carried out in two provinces in factors will be shown to lead to IM. In assessing gastric China with high and low cancer risks showed that cancer risk, histochemical typing of IM will most the prevalence of IM was much higher in an area with a high risk for gastric cancer.3 probably be replaced by molecular markers. .......................................................................... “IM in the stomach has a high cancer risk and is therefore defined as a precancerous SUMMARY condition” As intestinal metaplasia (IM) of the stomach is a risk factor in developing intestinal-type gastric Using a gastric cancer risk index, IM was the cancer, the question of reversibility is vital. The only criteria associated with the development of pathogenesis of gastric IM is being investigated intestinal-type gastric cancer in Japan.4 A long and it is likely that a combination of genetic term study concluded that there is an increased aspects of both Helicobacter pylori and the host, and risk of gastric cancer in subjects infected with H http://gut.bmj.com/ also environmental factors will be shown to cause pylori, severe gastric atrophy, body predominant this precancerous condition. There is emerging gastritis, or IM.5 Therefore, if IM is reversible, epidemiological evidence that with long term fol- there are tangible benefits in reduction in gastric low up (at least five years after H pylori cancer risk. eradication) IM may be reversible. Abolition of H pylori alone may not be the answer and combina- IF IM IS REVERSIBLE WE NEED TO tion with other chemopreventive agents may be UNDERSTAND THE PATHOGENESIS on September 30, 2021 by guest. Protected copyright. necessary. IM can be elusive and it is necessary to Of the different types of metaplasia in the undertake careful endoscopic evaluation and stomach, intestinal-type is the most common and biopsy likely sites (the lesser curve and angulus). it is associated with H pylori infection and bile In assessing gastric cancer risk, histochemical reflux.6 Experimentally, irradiation induces IM.7 typing of IM will probably be replaced by molecu- lar markers although neither of these at present H pylori and IM provides a better cancer risk index than simple H pylori has been implicated as a major cause of gastritis scores of antral and body mucosa and the IM. Two major studies provide epidemiological mere presence of IM. evidence for this. In a 10 year follow up of 35 patients with H pylori, IM progression was IS INTESTINAL METAPLASIA OF THE observed in 49% while no IM was seen during this STOMACH REVERSIBLE? time in non-infected patients.5 Another study of It is of fundamental importance to answer this 2455 individuals showed that IM was present in question—if IM of the stomach is reversible, 43.1% of H pylori positive patients compared with therapeutic intervention may be possible but if 6.2% of uninfected subjects. ....................... not, efforts can only be directed at prevention. “H pylori has been implicated as a major Correspondence to: However, in attempting to solve this issue, two M M Walker, Department major problems arise. Firstly, is the pathogenesis cause of IM” of Histopathology, Faculty of IM understood and therefore can intervention of Medicine, Imperial halt or reverse progression? Secondly, can we Atrophic gastritis and IM were strongly associ- College of Science, Technology and Medicine, diagnose and monitor the condition with any ated with H pylori and not with aging, leading to St Mary’s Campus, Norfolk degree of certainty? the conclusion that with a high prevalence of the Place, London W2 1PG, UK; [email protected] WHAT CAUSES IM AND WHY IS IT IMPORTANT THAT IT IS REVERSIBLE? ................................................. Accepted for publication 21 October 2002 Metaplasia is defined as a potentially reversible Abbreviations: IM, intestinal metaplasia; COX-2, ....................... change from a fully differentiated cell type to cyclooxygenase 2; MSI, microsatellite instability. www.gutjnl.com 2 Walker precursor lesion the risk of development of early gastric cancer precancerous process, mostly by increasing the rate of will continue to remain high in Japan.8 However, H pylori most regression of cancer precursor lesions.22 likely acts in concert with other factors to promote IM. Molecular events Gut: first published as 10.1136/gut.52.1.1 on 1 January 2003. Downloaded from Is it all in the genes? At the molecular level, the sequence of events is under inves- Recently, it has been shown that a variation in host and bacte- tigation. Microsatellite instability (MSI) is a genetic anomaly rial genetic background predisposes to the development of IM. in tumours and identified when alleles of novel sizes are There is evidence that IM is associated with cagA, functional detected in microsatellite sequences derived from cancer DNA oipA in H pylori, and IL-1RN 2 allele in patients from Italy,9 and that are not present in normal tissues of the same individual. another study on family risk of gastric cancer showed that first These can be detected in IM and the progressive accumulation degree relatives of patients with gastric cancer have an of MSI in areas of IM may contribute to gastric cancer increased prevalence of IM, which is strongly confined to development.23 MSI can be shown to be due to epigenetic those with H pylori infection.10 silencing of the hMLH1 gene caused by hypermethylation of a CpG island in the promoter region and was found recently to Other promoters of IM be an important cause of mismatch repair deficiency in 11 These include lack of vitamin C and cigarette smoking. The sporadic gastric cancer.24 Cyclins and cyclin dependent kinase concept of atrophy, subsequent hypochlorhydria with bacterial inhibitors play a crucial role in the control of cell cycle transi- overgrowth, and nitrate generation that damage DNA must also tions. Enhanced expression of cyclin D2 and reduced be considered. A European study showed that patients with IM expression of p27 have been implicated in the pathogenesis of had a significantly higher proportion of gastric juice samples cancer, and over expression of cyclin D2 and reduced expres- 12 containing bacteria and nitrite and had a gastric pH >6. The sion of p27 are closely linked to H pylori associated IM. Eradi- role of hypochlorhydria is interesting; studies in rats with IM cation of H pylori infection reverses the aberrant expression of induced by irradiation showed reversal following lowering of cyclin D2 and p27 in IM.25 These are potential areas for inter- 13 gastric pH. Bile is also a major factor in promotion of IM. An ventional strategies. early study from Leeds showed that after stratification for pre- vious surgery, age, and H pylori status, the histological feature “Expression of CDX2 may trigger the initiation and most strongly associated with bile reflux was IM, including all subtypes.6 Bile in combination with H pylori in rats promotes development of IM in the stomach” cyclooxygenase 2 (COX-2) expression in body mucosa and when bile was added, COX-2 expression in histologically normal In the gastrointestinal tract, homeobox genes regulate the appearing body mucosa was associated with cell proliferation, renewal of epithelium at given locations. CDX1 and CDX2 atrophy, and IM in the antrum.14 Sung et al also showed that genes are intestinal transcription factors that regulate both premalignant and malignant gastric lesions in human proliferation and differentiation of intestinal epithelial cells subjects demonstrate high COX-2 expression. Successful eradi- and the CDX1/2 protein is predominantly expressed in the cation of H pylori caused downregulation of COX-2 expression small intestine and colon but not in the normal adult stomach. 26 but failed to reverse IM at one year.15 These genes also have an important role in tumorigenesis. In IM, expression of CDX2 precedes those of CDX1, sucrase- http://gut.bmj.com/ EPIDEMIOLOGICAL EVIDENCE OF REVERSAL OF IM isomaltase, other intestine specific genes (human defensin 5, Does H pylori eradication reverse IM? alkaline phosphatase), and MUC2 during progression of IM. While this issue has been addressed extensively, there is no These findings imply that expression of CDX2 may trigger the 27 concerted view on regression following eradication of H initiation and development of IM in the stomach. pylori.16 A randomised one year follow up study reported that What switches on CDX1/2 genes in the stomach? The key 28 H pylori eradication was beneficial in preventing progression of here is possibly mesenchymal alteration. The inflammatory 17 atrophy and IM of the gastric mucosa and recent presenta- response to H pylori is also sited in mesenchyme and therefore on September 30, 2021 by guest.
Load more

Recommended publications
  • Short Course 10 Metaplasia in The
    0 3: 436-446 Rev Esp Patot 1999; Vol. 32, N © Prous Science, SA. © Sociedad Espajiola de Anatomia Patot6gica Short Course 10 © Sociedad Espafiola de Citologia Metaplasia in the gut Chairperson: NA. Wright, UK. Co-chairpersons: G. Coggi, Italy and C. Cuvelier, Belgium. Overview of gastrointestinal metaplasias only in esophagus but also in the duodenum, intestine, gallbladder and even in the pancreas. Well established is columnar metaplasia J. Stachura of esophageal squamous epithelium. Its association with increased risk of esophageal cancer is widely recognized. Recent develop- Dept. of Pathomorphology, Jagiellonian University ments have suggested, however, that only the intestinal type of Faculty of Medicine, Krakdw, Poland. metaplastic epithelium (classic Barrett’s esophagus) predisposes to cancer. Another field of studies is metaplasia in the short seg- ment at the esophago-cardiac junction, its association with Metaplasia is a reversible change in which one aduit cell type is Helicobacter pylon infection and/or reflux disease and intestinal replaced by another. It is always associated with some abnormal metaplasia in the cardiac and fundic areas. stimulation of tissue growth, tissue regeneration or excessive hor- Studies on gastric mucosa metaplasia could be divided into monal stimulation. Heterotopia, on the other hand, takes place dur- those concerned with pathogenesis and detailed structural/func- ing embryogenesis and is usually supposed not to be associated tional features and those concerned with clinical significance. with tissue damage. Pancreatic acinar cell clusters in pediatric gas- We know now that gastric mucosa may show not only complete tric mucosa form another example of aberrant cell differentiation. and incomplete intestinal metaplasia but also others such as ciliary Metaplasia is usually divided into epithelial and connective tis- and pancreatic metaplasia.
    [Show full text]
  • Subtypes of Intestinal Metaplasia and Helicobacter Pylorn Gut: First Published As 10.1136/Gut.33.5.597 on 1 May 1992
    Gut, 1992, 33, 597-600 597 Subtypes of intestinal metaplasia and Helicobacter pylorn Gut: first published as 10.1136/gut.33.5.597 on 1 May 1992. Downloaded from M E Craanen, P Blok, W Dekker, J Ferwerda, G N J Tytgat Abstract ing lesion, intestinal metaplasia are widely To determine whether there is a relationship recognised as being the most prevalent pre- between the presence of H pylon and the cursors of intestinal type gastric carcinoma.7 various subtypes ofintestinal metaplasia in the Subtypes of intestinal metaplasia have been gastric antrum, 2274 antral gastroscopic biop- identified based upon histological, ultra- sies from 533 patients were examined. Hpylon structural, enzyme, and mucin histochemical was found in 289 patients. Intestinal meta- characteristics. Some of the latter studies have plasia in general was found in 135 patients. suggested that a sulphomucin secreting, incom- Type I intestinal metaplasia was found in 133 plete intestinal metaplasia subtype is particularly patients (98.5%), type II in 106 patients (78.5%) closely linked to intestinal type gastric carcinoma and type III in 21 patients (15.6%). Ninety eight and may therefore be a marker of increased of these 135 patients (72.6%) were H pylori gastric cancer risk.8'~3 In another study evidence positive and 37 patients (27.4%) were H pylon was found for a strong association between the negative. No statistically significant difference presence of intestinal metaplasia in general and was found in the prevalence of type I and II H pylorn in the gastric antral mucosa.'4 We intestinal metaplasia between the intestinal undertook this study in order to investigate metaplasia positive and H pylon positive and further the relationship between the presence of intestinal metaplasia negative and H pylon H pylorn and the various subtypes of intestinal negative patients.
    [Show full text]
  • Histopathology of Barrett's Esophagus and Early-Stage
    Review Histopathology of Barrett’s Esophagus and Early-Stage Esophageal Adenocarcinoma: An Updated Review Feng Yin, David Hernandez Gonzalo, Jinping Lai and Xiuli Liu * Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA; fengyin@ufl.edu (F.Y.); hernand3@ufl.edu (D.H.G.); jinpinglai@ufl.edu (J.L.) * Correspondence: xiuliliu@ufl.edu; Tel.: +1-352-627-9257; Fax: +1-352-627-9142 Received: 24 October 2018; Accepted: 22 November 2018; Published: 27 November 2018 Abstract: Esophageal adenocarcinoma carries a very poor prognosis. For this reason, it is critical to have cost-effective surveillance and prevention strategies and early and accurate diagnosis, as well as evidence-based treatment guidelines. Barrett’s esophagus is the most important precursor lesion for esophageal adenocarcinoma, which follows a defined metaplasia–dysplasia–carcinoma sequence. Accurate recognition of dysplasia in Barrett’s esophagus is crucial due to its pivotal prognostic value. For early-stage esophageal adenocarcinoma, depth of submucosal invasion is a key prognostic factor. Our systematic review of all published data demonstrates a “rule of doubling” for the frequency of lymph node metastases: tumor invasion into each progressively deeper third of submucosal layer corresponds with a twofold increase in the risk of nodal metastases (9.9% in the superficial third of submucosa (sm1) group, 22.0% in the middle third of submucosa (sm2) group, and 40.7% in deep third of submucosa (sm3) group). Other important risk factors include lymphovascular invasion, tumor differentiation, and the recently reported tumor budding. In this review, we provide a concise update on the histopathological features, ancillary studies, molecular signatures, and surveillance/management guidelines along the natural history from Barrett’s esophagus to early stage invasive adenocarcinoma for practicing pathologists.
    [Show full text]
  • How Are We Addressing Gastric Intestinal Metaplasia?
    Editorial How are we addressing gastric intestinal metaplasia? Raúl A. Cañadas Garrido, MD1 1 Internist and Gastroenterologist at Hospital Universitario San Ignacio at the Pontificia The increasing sensitization of Colombian gastroenterologists to detection of early Universidad Javeriana, Postgraduate Coordinator gastric cancer is important not only for what it represents for patients prognoses but of Gastroenterology at the Pontificia Universidad Javeriana, Chief of Gastroenterology at Marly Clinic because of the therapeutic alternatives it opens the door to. These include endoscopic in Bogota, Colombia surgery which is less invasive than the already known and accepted surgical treatment .......................................... with intent to heal. Received: 10-11-12 It is clear for everyone that gastric cancer is still a public health problem and that most Accepted: 21-11-12 patients are diagnosed in advanced stages when there is rarely any option of healing. This makes us look back to the essential, back to screening programs and monitoring of high risk groups, and therefore back to identification of precancerous stages. The contribution of Dr. Pelayo Correa in describing the pathogenic sequence of intes- tinal gastric cancer, now accepted worldwide, shows how normal gastric mucosa, when confronted with environmental or hereditary factors, can evolve into superficial chronic gastritis, dysplasia and adenocarcinoma. It passes through intermediate stages such as atrophy and intestinal metaplasia which are considered to be preneoplastic stages, and then it evolves into gastric adenocarcinoma. The literature, however, is still uncertain regarding this final step. Here is where important questions begin to arise, “Which is more important for monitoring, keeping an eye on atrophy? Or watching the metaplasia?” In clinical practice we frequently show concern when monitoring metaplasia, but we do not look beyond or delve into the meaning of the term and its physiological and pathogenic implications.
    [Show full text]
  • Intestinal Metaplasia in Endoscopic Biopsy Specimens of Gastric Mucosa
    J Clin Pathol 1985;38:613-621 Intestinal metaplasia in endoscopic biopsy specimens of gastric mucosa GA ROTHERY, DW DAY From the Department ofPathology, University ofLiverpool, Liverpool SUMMARY A total of 1412 consecutive cases of endoscopic gastric biopsy, carried out over a four year period, were reviewed and specimens were examined histochemically to determine the prevalence of intestinal metaplasia and its variants. Three types were characterised: complete intestinal metaplasia and two classes of incomplete intestinal metaplasia (type hIa and type Ilb) depending on the absence or presence, respectively, of sulphomucins within mucin secreting columnar cells. Type lIb intestinal metaplasia was significantly more common in patients with gastric carcinoma (p < 0.001) and in those with dysplasia (p < 0.001) than in patients with benign gastric pathology. No such association was found with either type I or type hIa intestinal metaplasia. In addition to those present in the columnar cells of type IIb intestinal metaplasia, sulphomucins were also commonly found in goblet cells of all three types of metaplasia. The presence of sulphomucins in goblet cells, however, was not significantly associated with gastric carcinoma or dysplasia. The significance of the different types of intestinal metaplasia in relation to the pathological findings is discussed. Epidemiological, 2 and morphological3-5 studies or absence of large intestinal enzymes and mucins have shown that there is an association between (o-acylated sialomucins and sulphomucins). intestinal metaplasia and gastric carcinoma, and it Several recent studies show that the presence of has been considered by many to be a possible sulphated mucins in intestinal metaplasia has a marker of premalignant change.
    [Show full text]
  • The Transition from Gastric Intestinal Metaplasia to Gastric Cancer Involves POPDC1 and POPDC3 Downregulation
    International Journal of Molecular Sciences Article The Transition from Gastric Intestinal Metaplasia to Gastric Cancer Involves POPDC1 and POPDC3 Downregulation Rachel Gingold-Belfer 1,2,3,* , Gania Kessler-Icekson 1,3, Sara Morgenstern 4, Lea Rath-Wolfson 3,4, Romy Zemel 1,3, Doron Boltin 2,3, Zohar Levi 2,3 and Michal Herman-Edelstein 1,3,5 1 The Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva 4941492, Israel; [email protected] (G.K.-I.); [email protected] (R.Z.); [email protected] (M.H.-E.) 2 Rabin Medical Center, Gastroenterology Division, Petah Tikva 4941492, Israel; [email protected] (D.B.); [email protected] (Z.L.) 3 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; [email protected] 4 Rabin Medical Center, Department of Pathology, Petah Tikva 4941492, Israel; [email protected] 5 Rabin Medical Center, Department of Nephrology, Petah Tikva 4937211, Israel * Correspondence: [email protected]; Tel.: +972-52-2405895 Abstract: Intestinal metaplasia (IM) is an intermediate step in the progression from premalignant to malignant stages of gastric cancer (GC). The Popeye domain containing (POPDC) gene family encodes three transmembrane proteins, POPDC1, POPDC2, and POPDC3, initially described in muscles and later in epithelial and other cells, where they function in cell–cell interaction, and cell migration. POPDC1 and POPDC3 downregulation was described in several tumors, including colon and gastric cancers. We questioned whether IM-to-GC transition involves POPDC gene Citation: Gingold-Belfer, R.; dysregulation. Gastric endoscopic biopsies of normal, IM, and GC patients were examined for Kessler-Icekson, G.; Morgenstern, S.; expression levels of POPDC1-3 and several suggested IM biomarkers, using immunohistochemistry Rath-Wolfson, L.; Zemel, R.; Boltin, and qPCR.
    [Show full text]
  • The Diagnosis and Management of Achlorhydria
    The Diagnosis and Management of Achlorhydria Dicky Febrianto, Iswan Abbas Nusi, Poernomo Boedi Setiawan, Herry Purbayu, Titong Sugihartono, Ummi Maimunah, Ulfa Kholili, Budi Widodo, Amie Vidyani, Muhammad Miftahussurur and Husin Thamrin 1Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo Teaching Hospital, Surabaya, Indonesia [email protected] Keywords: Achlorhydria, kobalamin, vitamin, calcium Abstract: Achlorhydria is defined as a decrease in secretion quantity or decrease in the acidity of gastric acid. Gastric acid has several functions including activating other digestive enzymes, deciphering the food particles in the digestive process, essential vitamins and minerals absorption, and eliminating most of the microorganisms that enter with the food. There is no specific management for achlorhydria. Patients with achlorhydria in addition to experiencing disorders of HCl formation generally also suffer from pepsin deficiency. Therefore, pepsin is usually given to support the provision of betaine HCl. Patients with achlorhydria should be periodically monitored for early diagnosis of anemia due to iron deficiency and/or cobalamin. Calcium and vitamin D deficiency can be monitored through serum 25 hydroxyvitamin D level as well as bone density examination. 1 INTRODUCTION The signs that often arise include being weak, weary, lethargic due to anemia, the occurrence of Achlorhydria is a condition of decrease in the undigested food in the feces, neurological disorders, quantity or the absence of gastric acid (Schubert et and bone fractures (Fujita, 2014). al., 2013). The most common risk factor of The gold standard of achlorhydria diagnosis is achlorhydria is Helicobacter pylori infection. H. established by Heidelberg's gastric analysis pylori infection causes chronic atrophic gastritis technique to measure the acidity of gastric acid.
    [Show full text]
  • Management of Precancerous Conditions and Lesions in the Stomach
    74 Guideline Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED) Authors M. Dinis-Ribeiro*, 1,5, M. Areia2, 5, A. C. de Vries3, R. Marcos-Pinto4, 6, M. Monteiro-Soares5,A.O’Connor7, C. Pereira8, P. Pimentel-Nunes1, R. Correia5, A. Ensari†,9, J. M. Dumonceau‡,10, J. C. Machado11, G. Macedo§,12, P. Malfertheiner13, T. Matysiak-Budnik14, F. Megraud15, K. Miki16,C.O’Morain7, R. M. Peek17, T. Ponchon18, A. Ristimaki19, 20, B. Rembacken21, F. Carneiro¶,11, 22, E. J. Kuipers3 on behalf of MAPS Participants** (see below and Appendix) Institutions Institutions are listed at the end of article. Submitted: 4. August 2011 Atrophic gastritis, intestinal metaplasia, and epi- patients with precancerous conditions and le- Accepted after revision: thelial dysplasia of the stomach are common and sions of the stomach (termed MAPS). A multidis- 12. October 2011 are associated with an increased risk for gastric ciplinary group of 63 experts from 24 countries cancer. In the absence of guidelines, there is wide developed these recommendations by means of Bibliography disparity in the management of patients with repeat online voting and a meeting in June 2011 DOI http://dx.doi.org/ these premalignant conditions. The European So- in Porto, Portugal. The recommendations empha- 10.1055/s-0031-1291491 ciety of Gastrointestinal Endoscopy (ESGE), the size the increased cancer risk in patients with – Endoscopy 2012; 44: 74 94 European Helicobacter Study Group (EHSG), the gastric atrophy and metaplasia, and the need for © Georg Thieme Verlag KG European Society of Pathology (ESP) and the Soci- adequate staging in the case of high grade dyspla- Stuttgart · New York ISSN 0013-726X edade Portuguesa de Endoscopia Digestiva (SPED) sia, and they focus on treatment and surveillance have therefore combined efforts to develop evi- indications and methods.
    [Show full text]
  • Chronic Atrophic Gastritis: Don't Miss These Nutritional Deficiencies
    NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #197 NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #197 Carol Rees Parrish, MS, RDN, Series Editor Chronic Atrophic Gastritis: Don’t Miss These Nutritional Deficiencies Craig R. Gluckman Chronic atrophic gastritis (CAG) results in the destruction of gastric mucosa parietal cells leading to reduced gastric acid secretion and decreased intrinsic factor (IF) production. The consequence of which is achlorhydria, hypergastrinemia, and IF deficiency. As a result, CAG may lead to the malabsorption (albeit by different mechanisms) of vitamin B12 and iron, causing macrocytic anemia or iron deficiency anemia, respectively. Vitamin B12 deficiency, due to decreased IF production can result in megaloblastic anemia and varying neurologic dysfunction. The mechanism of iron deficiency in CAG is less clear but felt likely due to achlorhydria or concomitant Helicobacter pylori infection. In addition, other vitamin and micronutrient deficiencies (such as vitamin D, calcium and vitamin C) have been known to occur in patients with CAG, although the mechanisms for these have been less well studied. This article will review the nutritional deficiencies as a consequence of CAG. INTRODUCTION hronic atrophic gastritis (CAG) results in (H. pylori) infection. Regardless of the cause, the atrophy of the gastric body mucosa and the net effect of parietal cell loss and gastric atrophy Cchronic loss of gastric parietal cells. These is achlorhydria, which induces G cell hyperplasia parietal cells, under the influence of gastrin (from and the secretion of additional gastrin resulting in G cells) and histamine (from ECL cells), stimulate hypergastrinemia.2 Significantly, each of the above- acid production and lead to decreased pH in the mentioned causes of CAG harbor an increased gastric lumen.1 The parietal cells also control risk for gastric neoplasia, including gastric intrinsic factor (IF) production by a different adenocarcinoma and Type 1 gastric carcinoids, mechanism.
    [Show full text]
  • Columnar Mucosa and Intestinal Metaplasia of the Esophagus Fifty Years of Controversy
    ANNALS OF SURGERY REVIEW Vol. 231, No. 3, 303–321 © 2000 Lippincott Williams & Wilkins, Inc. Columnar Mucosa and Intestinal Metaplasia of the Esophagus Fifty Years of Controversy Steven R. DeMeester, MD,* and Tom R. DeMeester, MD† From the Departments of *Cardiothoracic Surgery and †Surgery, The University of Southern California School of Medicine, Los Angeles, California Objective esophageal reflux. Intestinal metaplasia, even a short To outline current concepts regarding etiology, diagnosis, and length, is premalignant, and the presence of dysplasia indi- treatment of intestinal metaplasia of the esophagus and cardia. cates progression on the pathway to adenocarcinoma. An- tireflux surgery, as opposed to medical therapy, may in- Summary Background Data duce regression or halt progression of intestinal Previously, endoscopic visualization of columnar mucosa ex- metaplasia. The presence of high-grade dysplasia is fre- tending a minimum of 3 cm into the esophagus was sufficient quently associated with an unrecognized focus of adeno- for the diagnosis of Barrett’s esophagus, but subsequently carcinoma. Vagal-sparing esophagectomy removes the the importance of intestinal metaplasia and the premalignant diseased esophagus and is curative in patients with high- nature of Barrett’s have been recognized. It is now apparent grade dysplasia. Invasion beyond the mucosa is associated that shorter lengths of intestinal metaplasia are common, and with a high likelihood of lymph node metastases and re- share many features of traditional 3-cm Barrett’s esophagus. quires lymphadenectomy. Methods Themes and concepts pertaining to intestinal metaplasia of the esophagus and cardia are developed based on a review Conclusions of the literature published between 1950 and 1999.
    [Show full text]
  • Pathways of Gastric Carcinogenesis, Helicobacter Pylori Virulence and Interactions with Antioxidant Systems, Vitamin C and Phytochemicals
    International Journal of Molecular Sciences Review Pathways of Gastric Carcinogenesis, Helicobacter pylori Virulence and Interactions with Antioxidant Systems, Vitamin C and Phytochemicals James W. T. Toh 1 and Robert B. Wilson 2,* 1 University of Sydney, UNSW, Westmead Hospital, Sydney, NSW 2145, Australia; [email protected] 2 Department of Upper Gastrointestinal Surgery, UNSW, Liverpool Hospital, Liverpool, NSW 2170, Australia * Correspondence: [email protected] Received: 1 August 2020; Accepted: 31 August 2020; Published: 3 September 2020 Abstract: Helicobacter pylori is a class one carcinogen which causes chronic atrophic gastritis, gastric intestinal metaplasia, dysplasia and adenocarcinoma. The mechanisms by which H. pylori interacts with other risk and protective factors, particularly vitamin C in gastric carcinogenesis are complex. Gastric carcinogenesis includes metabolic, environmental, epigenetic, genomic, infective, inflammatory and oncogenic pathways. The molecular classification of gastric cancer subtypes has revolutionized the understanding of gastric carcinogenesis. This includes the tumour microenvironment, germline mutations, and the role of Helicobacter pylori bacteria, Epstein Barr virus and epigenetics in somatic mutations. There is evidence that ascorbic acid, phytochemicals and endogenous antioxidant systems can modify the risk of gastric cancer. Gastric juice ascorbate levels depend on dietary intake of ascorbic acid but can also be decreased by H. pylori infection, H. pylori CagA secretion, tobacco smoking, achlorhydria and chronic atrophic gastritis. Ascorbic acid may be protective against gastric cancer by its antioxidant effect in gastric cytoprotection, regenerating active vitamin E and glutathione, inhibiting endogenous N-nitrosation, reducing toxic effects of ingested nitrosodimethylamines and heterocyclic amines, and preventing H. pylori infection. The effectiveness of such cytoprotection is related to H.
    [Show full text]
  • Gastritis and Carditis David A
    Gastritis and Carditis David A. Owen, M.B. University of British Columbia, Vancouver, British Columbia, Canada ations. Carditis is a controversial topic: currently Dyspepsia is a common clinical problem. Its causes opinions are divided as to whether it is the result of include peptic ulcer disease, gastroesophageal re- gastroesophageal reflux or a proximal extension of flux, and functional (nonulcer) dyspepsia. A detailed H. pylori infection from the remainder of the clinical description of pain does not reliably differ- stomach. entiate the cause. Approximately 80% of gastrosco- pies are performed for the investigation of dyspep- KEY WORDS: Atrophic gastritis, Carditis, Gastric sia. “Gastritis” is diagnosed endoscopically in 59% cardia, Gastric Crohn’s disease, Gastritis, Helicobac- of all stomachs, although in only 3% are the changes ter, Lymphocytic gastritis, Pernicious anemia, Pro- severe. Pathologic examination of unselected gas- ton pump inhibitors, Reactive gastropathy. tric biopsy specimens reveals that abnormalities are Mod Pathol 2003;16(4):325–341 present in 62–73%, but there is only a weak corre- lation between endoscopic and histologic findings. Most gastroscopies are performed for the investiga- For these reasons, it is recommended that endo- tion of dyspepsia (1–7). This is a common clinical scopic examination should always be accompanied problem but is rarely life-threatening. The causes of by biopsy. Ideally, biopsies should be taken in a dyspepsia include peptic ulcer disease (30%), gas- systematic fashion to include sampling of antrum troesophageal reflux (29%), and nonulcer (func- and corpus. Recent evidence suggests that gastric tional) dyspepsia (40%). The cause of functional infection by Helicobacter pylori initially presents as dyspepsia is unclear at the present time, although a superficial gastritis.
    [Show full text]