Food-Specific IgG4 Is Elevated Throughout the Upper Gastrointestinal Tract in Eosinophilic Esophagitis.

BACKGROUND: Food-specific immunoglobulin G4 (FS-IgG4) is associated with eosinophilic esophagitis (EoE); however, it is not clear whether production is limited to the esophagus. AIMS: To assess FS-IgG4 levels in the upper gastrointestinal tract and plasma and compare these with endoscopic disease severity, tissue eosinophil counts, and patient-reported symptoms. METHODS: We examined prospectively banked plasma, throat swabs, and upper gastrointestinal biopsies (esophagus, gastric antrum, and duodenum) from control (n = 15), active EoE (n = 24), and inactive EoE (n = 8) subjects undergoing upper endoscopy. Patient-reported symptoms were assessed using the EoE symptom activity index (EEsAI). Endoscopic findings were evaluated using the EoE endoscopic reference score (EREFS). Peak eosinophils per high-power field (eos/hpf) were assessed from esophageal biopsies. Biopsy homogenates and throat swabs were normalized for protein content and assessed for FS-IgG4 to milk, wheat, and egg. RESULTS: Median FS-IgG4 for milk and wheat was significantly increased in the plasma, throat swabs, esophagus, stomach, and duodenum of active EoE subjects compared to controls. No significant differences for milk- or wheat-IgG4 were observed between active and inactive EoE subjects. Among the gastrointestinal sites sampled, FS-IgG4 levels were highest in the esophagus. Esophageal FS-IgG4 for all foods correlated significantly across all sites sampled (r ≥ 0.59, p < 0.05). Among subjects with EoE, esophageal FS-IgG4 correlated significantly with peak eos/hpf (milk and wheat) and total EREFS (milk). EEsAI scores and esophageal FS-IgG4 levels did not correlate. CONCLUSIONS: Milk and wheat FS-IgG4 levels are elevated in plasma and throughout the upper gastrointestinal tract in EoE subjects and correlate with endoscopic findings and esophageal eosinophilia.

Gastrointestinal Kaposi Sarcoma Involving Stomach and Colon: Diagnostic Pitfall for Pathologists with Expression of CD117.

Kaposi sarcoma (KS) is a low-grade vascular tumor caused by human herpes virus type 8 (HHV8). Gastrointestinal involvement of KS is rare and most commonly clinically silent. Gastrointestinal KS may mimic gastrointestinal stromal tumors (GISTs) histologically as the tumor formed by morphologically spindle-shaped cells, which is mostly located in the mucosa and submucosa. In the present study, we describe a case of Kaposi sarcoma that was first diagnosed in the gastrointestinal tract of a 73-year-old female patient who presented to the clinic with nausea and diarrhea. Immunohistochemical staining showed cytoplasmic CD117 expression both in stomach and colon biopsies. Although involvement of KS is rarely seen in the gastrointestinal tract (GIT), the differential diagnosis of low-grade spindle cell lesions without significant pleomorphism, KS should definitely be considered, and it should be known that CD117 positivity is also present in these neoplasms.

Human gastrointestinal epithelia of the esophagus, stomach, and duodenum resolved at single-cell resolution.

The upper gastrointestinal tract, consisting of the esophagus, stomach, and duodenum, controls food transport, digestion, nutrient uptake, and hormone production. By single-cell analysis of healthy epithelia of these human organs, we molecularly define their distinct cell types. We identify a quiescent COL17A1high KRT15high stem/progenitor cell population in the most basal cell layer of the esophagus and detect substantial gene expression differences between identical cell types of the human and mouse stomach. Selective expression of BEST4, CFTR, guanylin, and uroguanylin identifies a rare duodenal cell type, referred to as BCHE cell, which likely mediates high-volume fluid secretion because of continual activation of the CFTR channel by guanylin/uroguanylin-mediated autocrine signaling. Serotonin-producing enterochromaffin cells in the antral stomach significantly differ in gene expression from duodenal enterochromaffin cells. We, furthermore, discover that the histamine-producing enterochromaffin-like cells in the oxyntic stomach express the luteinizing hormone, yet another member of the enteroendocrine hormone family.

Recent advances upper gastrointestinal lymphomas: molecular updates and diagnostic implications.

Approximately one-third of extranodal non-Hodgkin lymphomas involve the gastrointestinal (GI) tract, with the vast majority being diagnosed in the stomach, duodenum, or proximal small intestine. A few entities, especially diffuse large B-cell lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, represent the majority of cases. In addition, there are diseases specific to or characteristic of the GI tract, and any type of systemic lymphoma can present in or disseminate to these organs. The recent advances in the genetic and molecular characterisation of lymphoid neoplasms have translated into notable changes in the classification of primary GI T-cell neoplasms and the recommended diagnostic approach to aggressive B-cell tumours. In many instances, diagnoses rely on morphology and immunophenotype, but there is an increasing need to incorporate molecular genetic markers. Moreover, it is also important to take into consideration the endoscopic and clinical presentations. This review gives an update on the most recent developments in the pathology and molecular pathology of upper GI lymphoproliferative diseases.

Plasma membrane Ca2+-permeable channels and sodium/calcium exchangers in tumorigenesis and tumor development of the upper gastrointestinal tract.

The upper gastrointestinal (GI) tumors are multifactorial diseases associated with a combination of oncogenes and environmental factors. Currently, surgery, chemotherapy, radiotherapy and immunotherapy are relatively effective treatment options for the patients with these tumors. However, the asymptomatic phenotype of these tumors during the early stages poses as a significant limiting factor to diagnosis and often renders treatments ineffective. Therefore, new early diagnosis and effective therapy for upper GI tumors are urgently needed. Ca2+ is a pivotal intracellular second messenger and plays a crucial role in living cells by regulating several processes from cell division to death. The aberrant Ca2+ homeostasis is related to many human pathological conditions and diseases, including cancer, and thus the changes in the expression and function of plasma membrane Ca2+ permeable channels and sodium/calcium exchangers are frequently described in tumorigenesis and tumor development of the upper GI tract, including voltage-gated Ca2+ channels (VGCC), transient receptor potential (TRP) channels, store-operated channels (SOC) and Na+/Ca2+ exchanger (NCX). This review will summarize the current knowledge about plasma membrane Ca2+ permeable channels and sodium/calcium exchangers in the upper GI tumors and provide a synopsis of recent advancements on the role and involvement of these channels in upper GI tumors as well as a discussion of the possible strategies to target these channels and exchangers for diagnosis and therapy of the upper GI tumors.

Sympathetic Denervation of the Common Hepatic Artery Lessens Glucose Intolerance in the Fat- and Fructose-Fed Dog.

This study assessed the effectiveness of surgical sympathetic denervation of the common hepatic artery (CHADN) in improving glucose tolerance. CHADN eliminated norepinephrine content in the liver and partially decreased it in the pancreas and the upper gut. We assessed oral glucose tolerance at baseline and after 4 weeks of high-fat high-fructose (HFHF) feeding. Dogs were then randomized to sham surgery (SHAM) (n = 9) or CHADN surgery (n = 11) and retested 2.5 or 3.5 weeks later while still on the HFHF diet. CHADN improved glucose tolerance by ∼60% in part because of enhanced insulin secretion, as indicated by an increase in the insulinogenic index. In a subset of dogs (SHAM, n = 5; CHADN, n = 6), a hyperinsulinemic-hyperglycemic clamp was used to assess whether CHADN could improve hepatic glucose metabolism independent of a change in insulin release. CHADN reduced the diet-induced defect in net hepatic glucose balance by 37%. In another subset of dogs (SHAM, n = 4; CHADN, n = 5) the HFHF diet was continued for 3 months postsurgery and the improvement in glucose tolerance caused by CHADN continued. In conclusion, CHADN has the potential to enhance postprandial glucose clearance in states of diet-induced glucose intolerance.

Immunohistochemical expression of Ki-67 and p53 along with their digitalized evaluation in the discriminatory analysis of reactive atypia and dysplastic lesions in gastrointestinal biopsies of the stomach.

The differential diagnosis between reactive atypia and non-invasive neoplasia (or dysplasia) can be challenging in the case of small conventional forceps biopsy specimens of the stomach. Despite the existence of several classifications for neoplastic epithelial lesions of the stomach, there are few auxiliary tools for aiding in this decision besides standard stains. We studied the utility of Ki-67 and p53 immunohistochemistry in this setting and their clinico-pathological correlations, based on a set of 99 cases with cytological or architectural atypia reviewed by three pathologists. We also tested a digitalized method based on the ImageJ software for the evaluation of Ki-67 expression to determine whether this could be of an additional help. CONCLUSIONS: Ki-67 and p53 expression correlates well with microscopic and morphological modifications in biopsies and can be a useful tool in confirming or dismissing an impression of dysplasia in routine pathological work-up. Digital processing is cumbersome and of limited value and it could only be of additional help if more automated methods are developed.

Establishment of patient-derived xenograft models and cell lines for malignancies of the upper gastrointestinal tract.

BACKGROUND: The upper gastrointestinal tract is home to some of most notorious cancers like esophagogastric and pancreatic cancer. Several factors contribute to the lethality of these tumors, but one that stands out for both tumor types is the strong inter- as well as intratumor heterogeneity. Unfortunately, genetic tumor models do not match this heterogeneity, and for esophageal cancer no adequate genetic models exist. To allow for an improved understanding of these diseases, tissue banks with sufficient amount of samples to cover the extent of diversity of human cancers are required. Additionally, xenograft models that faithfully mimic and span the breadth of human disease are essential to perform meaningful functional experiments. METHODS: We describe here the establishment of a tissue biobank, patient derived xenografts (PDXs) and cell line models of esophagogastric and pancreatic cancer patients. Biopsy material was grafted into immunocompromised mice and PDXs were used to establish primary cell cultures to perform functional studies. Expression of Hedgehog ligands in patient tumor and matching PDX was assessed by immunohistochemical staining, and quantitative real-time PCR as well as flow cytometry was used for cultured cells. Cocultures with Hedgehog reporter cells were performed to study paracrine signaling potency. Furthermore, SHH expression was modulated in primary cultures using lentiviral mediated knockdown. RESULTS: We have established a panel of 29 PDXs from esophagogastric and pancreatic cancers, and demonstrate that these PDXs mirror several of the (immuno)histological and biochemical characteristics of the original tumors. Derived cell lines can be genetically manipulated and used to further study tumor biology and signaling capacity. In addition, we demonstrate an active (paracrine) Hedgehog signaling mode by both tumor types, the magnitude of which has not been compared directly in previous studies. CONCLUSIONS: Our established PDXs and their matching primary cell lines retain important characteristics seen in the original tumors, and this should enable future studies to address the responses of these tumors to different treatment modalities, but also help in gaining mechanistic insight in how some tumors respond to certain regimens and others do not.

Targeting c-MET/HGF signaling pathway in upper gastrointestinal cancers: rationale and progress.

Aberrant activation of receptor-tyrosine kinase c-Met/HGF pathway is shown to be associated with cell proliferation, invasion, metastasis and poor-prognosis in several tumor types, including upper gastrointestinal-malignancies. The interaction of c-Met with multiple signalling-pathways involved in tumorigenic-properties and invasive-phenotype has gained substantial attention, suggesting its role as an intriguing-target for cancer-therapy. In recent years, there have been considerable efforts in the development of effective c-Met inhibitors with potential clinical-applications and one of them, crizotinib (dual c-Met/ALK inhibitor), has recently been approved for lung-cancers with ALKrearrangement. However several important questions remain to be answered on the molecular mechanisms underlying the antitumor effects of crizotinib, as well as on its possible role in the treatment of different tumor types, including uppergastrointestinal- cancers. The aim of this review is to give an overview on critical role of the c-Met/HGF pathway in cancer, and the preclinical/clinical studies on c-Met inhibitors. There are accumulating evidences on therapeutic potential of c-Met inhibitors for the treatment of other malignancies, such as gastric and pancreatic cancers. However, further investigations are needed to identify determinants of the activity of c-Met inhibitors, through the analysis of genetic/ environmental alterations affecting c-Met and parallel pro-cancer pathways; mechanisms result in developing resistance to anti-c-Met agents; and selection of patients that might benefit from therapy. These studies will be essential to improve the selectivity/efficacy of future anticancer strategies of c-Met targeted-therapies in the treatment of upper gastrointestinal- cancers.

Clinical trial of ghrelin synthesis administration for upper GI surgery.

Appetite and weight loss following gastrectomy or esophagectomy is one of the major problems that affect the postoperative QoL. Ghrelin, mainly secreted from the stomach, is related to appetite, weight gain, and positive energy balance. This hormone level had been shown to become low for a long time after upper GI surgery. The efficacy of ghrelin synthesis administration for postoperative weight loss was investigated from a clinical trial to develop a new strategy for weight gain. In addition to this treatment for appetite and weight loss, we focused on the anti-inflammatory role of ghrelin. For the purpose of controlling postoperative cytokine storm after esophagectomy, this hormone was introduced in the clinical trial. Finally, ghrelin replacement therapy during chemotherapy in patients with esophageal cancer is also presented. Our clinical trials and their results are presented in this chapter.

Development of photostable gastro retentive formulation for nifedipine using low-density polypropylene microporous particles.

The aim of this study was to develop photostable gastro retentive formulation for nifedipine loading into low-density polypropylene microporous particles (Accurel MP 1000®) by a solvent evaporation technique using the 3² factorial design. Yield, drug loading, surface topography, thermal properties, crystal characteristics, photostability and in vitro drug release were studied. Optimized microparticles formulated into a capsule were evaluated for the dissolution study and compared with marketed formulation. Higher values of T(50%), time required for 50% degradation of drug with threefold and 1.5-fold decrease in degradation rate constant (K) under UV and fluorescent lamp were observed for the microparticles, respectively, as compared to pure nifedipine indicated remarkable improved photostability. Microparticles showed good floating ability in 0.1N HCl with initial burst release (16-29%) followed by the zero-order drug release up to 8 h. The capsule formulation followed the ideal modified release pattern.

T-cell-mediated tumor immune surveillance and expression of B7 co-inhibitory molecules in cancers of the upper gastrointestinal tract.

Tumorigenesis can induce adaptive T-cell-mediated immune responses against malignant cells. Such cellular immune responses are actively suppressed by cancer cells via mechanisms of immune tolerance. We studied T-cell responses against tumor growth by examining tumor-infiltrating lymphocytes (TILs) in upper gastrointestinal (GI) cancers. The number of T-bet(+) TILs correlates with better survival of esophageal cancer patients. Using well-defined mouse models, we have further shown that T-bet and Eomes are both required for the adaptive anti-tumor immunity by regulating T-cell trafficking into the tumor tissue and their effector functions inside the tumor microenvironment. In order to gain further insight into the tumor immune microenvironment in the upper GI cancer, we have also studied expression levels of co-inhibitory molecules such as B7-H1/PD-L1 and B7-H4 in tissue specimens of esophageal and gastric cancers. These inhibitory B7 molecules were expressed at high but variable levels by cancer cells. The overexpression of these molecules correlates with poor clinicopathological parameters and shorter patient survival time. The number of CD3(+) and CD8(+) TILs correlates inversely with expression levels of B7-H4 in samples from esophageal cancer, supporting a role of active immune suppression by inhibitory B7 molecules in the tumor microenvironment. In addition, TILs show functional exhaustion and express high levels of PD-1 and Tim-3. We propose that metabolic competition mediated by phosphatidylinositol 3-kinases (PI3Ks) characterizes the immune suppression within cancer tissues. Future tumor vaccine design should combine blockade of B7 inhibitory molecules and enhancement of T-bet and Eomes levels within the tumor microenvironment.

Proteomic analysis of urinary upper gastrointestinal cancer markers.

PURPOSE: We have investigated the use of human urine as a non-invasive medium to screen for molecular biomarkers of carcinomas of the upper gastrointestinal (uGI) tract using SELDI-TOF-MS. EXPERIMENTAL DESIGN: A total of 120 urine specimens from 60 control and 60 uGI cancer patients were analysed to establish a potential biomarker fingerprint for the weak cation exchanger CM10 chip surface, which was validated by blind testing using a further 59 samples from 33 control and 26 uGI cancer patients. RESULTS: Using Biomarker Pattern software, we established a model with a sensitivity of 98% and specificity of 95% for the learning sample set, and a sensitivity of 96% and specificity of 72% for the validation data set. Model variable importance included six peptides with m/z of 10,230, 10,436, 10,574, 10,311, 10,467, and 10,118 of which the 10, 230 molecular species was the main decider (sensitivity 86% and specificity 80%). Initial protein database searching identified 10,230 as S100-A6, 10,436 as S100-P, 10,467 as S100-A9, and 10,574 as S100-A12 of which S100-A6 and S100-A9 were confirmed by Western blotting. CONCLUSIONS AND CLINICAL RELEVANCE: We have demonstrated that SELDI-TOF-MS as a screening tool is a rapid and valid methodology in the search for urinary cancer biomarkers, and is potentially useful in defining and consolidating biomarker patterns for uGI cancer screening.

Regulation of ß-catenin by t-DARPP in upper gastrointestinal cancer cells.

BACKGROUND: Truncated dopamine and cyclic-AMP-regulated phosphoprotein (t-DARPP) is frequently overexpressed in gastrointestinal malignancies. In this study, we examined the role of t-DARPP in regulating ß-catenin. RESULTS: The pTopFlash construct that contains multiple TCF/LEF-binding sites was used as a measure of ß-catenin/TCF transcription activity. Gastric (AGS, MKN28) and esophageal (FLO-1) adenocarcinoma cancer cell lines that lack t-DARPP expression were utilized to establish stable and transient in vitro expression models of t-DARPP. The expression of t-DARPP led to a significant induction of the pTOP reporter activity, indicative of activation of ß-catenin/TCF nuclear signaling. Immunofluorescence assays supported this finding and showed accumulation and nuclear translocation of ß-catenin in cells expressing t-DARPP. These cells had a significant increase in their proliferative capacity and demonstrated up-regulation of two transcription targets of ß-catenin/TCF: Cyclin D1 and c-MYC. Because phosphorylated GSK-3ß is inactive and loses its ability to phosphorylate ß-catenin and target it towards degradation by the proteasome, we next examined the levels of phospho-GSK-3ß. These results demonstrated an increase in phospho-GSK-3ß and phospho-AKT. The knockdown of endogenous t-DARPP in MKN45 cancer cells demonstrated a reversal of the signaling events. To examine whether t-DARPP mediated GSK-3ß phosphorylation in an AKT-dependent manner, we used a pharmacologic inhibitor of PI3K/AKT, LY294002, in cancer cells expressing t-DARPP. This treatment abolished the phosphorylation of AKT and GSK-3ß leading to a reduction in ß-catenin, Cyclin D1, and c-MYC protein levels. CONCLUSIONS: Our findings demonstrate, for the first time, that t-DARPP regulates ß-catenin/TCF activity, thereby implicating a novel oncogenic signaling in upper gastrointestinal cancers.

Oral administration of tributyrin increases concentration of butyrate in the portal vein and prevents lipopolysaccharide-induced liver injury in rats.

BACKGROUND & AIMS: Short-chain fatty acids, especially butyrate, have various biological activities including inhibition of tumor necrosis factor (TNF)-α secretion, via attenuation of nuclear factor-κB (NF-κB) activation. Here, we evaluated the protective effect of oral administration of tributyrin, a prodrug of butyrate, on lipopolysaccharide (LPS)-induced liver injury in rats. METHODS: Rats were divided into four groups: normal control, tributyrin, LPS, and tributyrin/LPS (treated with tributyrin 1 h before LPS). Plasma levels of butyrate and TNF-α, expression of TNF-α, NF-κB, Toll-like receptor (TLR) 2, and TLR4 mRNA in liver, blood biochemical tests, and histopathological analysis of liver were performed. RESULTS: Oral tributyrin increased plasma butyrate level in the portal vein to 2.4 mM at 1 h and 0.7 mM at 2.5 h. Tributyrin attenuated NF-κB activation and liver tissue injury associated with LPS injection. The increases in TNF-α level, and hepatic TLR2 mRNA expression were lower in the tributyrin/LPS group. We believe that this study provides the first evidence that orally administered tributyrin increases butyrate level in the hepato-portal system and attenuates liver injury and subsequent inflammatory responses. CONCLUSION: Oral tributyrin increased plasma butyrate in the portal vein and attenuated liver injury in endotoxemic rats.

Salivary epithelial cells: an unassuming target site for gene therapeutics.

Salivary glands are classical exocrine glands whose external secretions result in the production of saliva. However, in addition to the secretion of exocrine proteins, salivary epithelial cells are also capable of secreting proteins internally, into the bloodstream. This brief review examines the potential for using salivary epithelial cells as a target site for in situ gene transfer, with an ultimate goal of producing therapeutic proteins for treating both systemic and upper gastrointestinal tract disorders. The review discusses the protein secretory pathways reported to be present in salivary epithelial cells, the viral gene transfer vectors shown useful for transducing these cells, model transgenic secretory proteins examined, and some clinical conditions that might benefit from such salivary gland gene transfer.

Luminal chemosensing and upper gastrointestinal mucosal defenses.

The upper gastrointestinal mucosa is exposed to endogenous and exogenous substances, including gastric acid, carbon dioxide, and foodstuffs. Physiologic processes such as secretion, digestion, absorption, and motility occur in the gastrointestinal tract in response to ingested substances, which implies the presence of mucosal sensors. We hypothesize that mucosal acid sensors and tastelike receptors are important components of the mucosal chemosensing system. We have shown that luminal acid/carbon dioxide is sensed via ecto- and cytosolic carbonic anhydrases and ion transporters in the epithelial cells and via acid sensors on the afferent nerves in the duodenum and esophagus. Furthermore, a luminal l-glutamate signal is mediated via mucosal l-glutamate receptors with activation of afferent nerves and cyclooxygenase in the duodenum, which suggests the presence of luminal l-glutamate sensing. These luminal chemosensors help to activate mucosal defense mechanisms to maintain the mucosal integrity and physiologic responses of the upper gastrointestinal tract. Because neural pathways are components of the luminal chemosensory system, investigation of these pathways may help to identify novel molecular targets in the treatment and prevention of mucosal injury and visceral sensation.

Carcinomas of the upper aerodigestive tract with rearrangement of the nuclear protein of the testis (NUT) gene (NUT midline carcinomas).

This manuscript reviews carcinomas of the upper aerodigestive tract associated with genetic rearrangements of the nuclear protein of the testis (NUT) gene, also known as NUT midline carcinomas. The literature is reviewed regarding all reported cases of NUT midline carcinomas and the clinicopathologic features are discussed. Our current understanding of the molecular pathogenesis of the disease is also discussed, along with the differential diagnosis for undifferentiated or poorly differentiated malignancy of the upper aerodigestive tract.

Exhaled ethane concentration in patients with cancer of the upper gastrointestinal tract - a proof of concept study.

There has been growing interest in the measurement of breath ethane as an optimal non-invasive marker of oxidative stress. High concentrations of various breath alkanes including ethane have been reported in a number of malignancies. Our aim was to investigate the use of novel laser spectroscopy for rapid reporting of exhaled ethane and to determine whether breath ethane concentration is related to a diagnosis of upper gastrointestinal malignancy. Two groups of patients were recruited. Group A (n = 20) had a histo-pathological diagnosis of either esophageal or gastric malignancy. Group B (n = 10) was made up of healthy controls. Breath samples were collected from these subjects and the ethane concentration in these samples was subsequently measured to an accuracy of 0.2 parts per billion, ppb. Group A patients had a corrected exhaled breath ethane concentration of 2.3 +/- 0.8 (mean +/- SEM) ppb. Group B patients registered a mean of 3.1 +/- 0.5 ppb. There was no statistically significant difference between the two groups (p = 0.39). In conclusion, concentrations of ethane in collected breath samples were not significantly elevated in upper gastrointestinal malignancy. The laser spectroscopy system provided a reliable and rapid turnaround for breath sample analysis.

Iron-induced mucosal pathology of the upper gastrointestinal tract: a common finding in patients on oral iron therapy.

AIMS: Upper gastrointestinal injury from iron tablets at therapeutic dose is not widely recognized. The aim was to document cases of iron-related upper gastrointestinal (GI) pathology and to determine frequency of occurrence. METHODS AND RESULTS: We prospectively studied patients with iron deficiency anaemia undergoing upper GI endoscopy from November 2005 to July 2006. Cases of upper GI iron deposition from these and other cases extracted retrospectively between 1999 and 2006 were examined histopathologically and patient notes were reviewed. In the prospective study, 15/160 patients investigated for iron deficiency anaemia [16.1% (15/93) of those taking oral iron tablets] had iron deposition noted on routine haematoxylin and eosin staining. In this plus the retrospective series, 59 patients were identified with 64 episodes of iron deposition. Eighty-six percent (6/7) with oesophageal iron deposition had associated erosion. Sixty-three percent (29/46) with gastric iron deposition had erosion and 80% (37/46) had reactive gastritis. Duodenal deposition was usually (91%, 10/11) within macrophages in villous tips with no erosion. Ninety-eight percent (58/59) of iron deposition cases had documented oral iron intake. CONCLUSIONS: Iron deposition in the upper GI tract is common in patients taking iron tablets. It is frequently associated with mucosal disruption in the oesophagus and stomach.