Intestinal Epithelial Dysplasia Research Articles

T cell migration and effector function differences in familial adenomatous polyposis patients with APC gene mutations.

Familial adenomatous polyposis (FAP) is an inherited disease characterized by the development of large number of colorectal adenomas with high risk of evolving into colorectal tumors. Mutations of the Adenomatous polyposis coli (APC) gene is often at the origin of this disease, as well as of a high percentage of spontaneous colorectal tumors. APC is therefore considered a tumor suppressor gene. While the role of APC in intestinal epithelium homeostasis is well characterized, its importance in immune responses remains ill defined. Our recent work indicates that the APC protein is involved in various phases of both CD4 and CD8 T cells responses. This prompted us to investigate an array of immune cell features in FAP subjects carrying APC mutations. A group of 12 FAP subjects and age and sex-matched healthy controls were studied. We characterized the immune cell repertoire in peripheral blood and the capacity of immune cells to respond ex vivo to different stimuli either in whole blood or in purified T cells. A variety of experimental approaches were used, including, pultiparamater flow cytometry, NanosString gene expression profiling, Multiplex and regular ELISA, confocal microscopy and computer-based image analyis methods. We found that the percentage of several T and natural killer (NK) cell populations, the expression of several genes induced upon innate or adaptive immune stimulation and the production of several cytokines and chemokines was different. Moreover, the capacity of T cells to migrate in response to chemokine was consistently altered. Finally, immunological synapses between FAP cytotoxic T cells and tumor target cells were more poorly structured. Our findings of this pilot study suggest that mild but multiple immune cell dysfunctions, together with intestinal epithelial dysplasia in FAP subjects, may facilitate the long-term polyposis and colorectal tumor development. Although at an initial discovery phase due to the limited sample size of this rare disease cohort, our findings open new perspectives to consider immune cell abnormalities into polyposis pathology.

Naïve T Cell-Depleted Hematopoietic Graft Combined with Solid Organ Transplantation As Strategy to Induce Tolerance By Transient Mixed Chimerism

BACKGROUND The major challenge of solid organ transplantation (SOT) is to prevent graft rejection. The chronic use of pharmacological immunosuppression has been associated with increased rates of infection, cardiovascular, metabolic, endocrine disorders, and cancer. The induction of chimerism by donor hematopoietic stem cell transplantation (HSCT) together with SOT is an active tolerance induction approach. Here, we present a new model for inducing transient mixed chimerism in 2 patients undergoing SOT employing a non-myeloablative conditioning (NMA) regimen and a partially T cell-depleted (TCD) graft consisting of CD34+ hematopoietic progenitor cells and CD45RA− memory lymphocytes. METHODS SOT and HSCT were performed at University Hospital La Paz, Madrid. Bone marrow harvesting was performed on the iliac crest and lumbar and dorsal vertebrae of the deceased donor for patient#1 and mobilized leukoapheresis from sibling donor for patient#2. First we obtained the enriched by CD34+ selection using the CliniMACS system (Miltenyi Biotec) and afterwards the CD45RA− cells were purified. Lineage-specific chimerism analysis was analyzed using quantitative real-time polymerase chain reaction. Immune cell recovery was monitored by multiparametric flow cytometry. We obtained the permission of the Organización Nacional de Trasplantes and the informed consent was obtained from the patient and donor and/or caregivers. RESULTSPatient 1 A 15-year-old boy was diagnosed with intestinal epithelial dysplasia in 2008. After two previous intestinal and multivisceral acute cellular rejections forced a third MVT. With the imptemption to induce donor tolerance, a T cell-depleted bone marrow graft from the same deceased donor was employed. Bone marrow harvesting was performed obtaining a total volume of 141 ml with 4x109 total nucleated cells. Peripheral blood was obtained after unclasping the thoracic aorta. The stem cell fraction from bone marrow was enriched by CD34+ selection, obtaining 8.75x105/kg CD34+cells/kg. Memory lymphocytes were purified and aliquots containing 1x106/kg CD3+CD45RO+ and 2.1x104/kg CD3+CD45RA+ T cells. Both products were cryopreserved. The conditioning regimen before HSCT included fludarabine and cyclophosphamide. On day 88 after MVT, we infused all the CD34+ cells and 1x106/Kg CD3+CD45RO+ T cells. The CD3+CD45RO+ T cells were also infused periodically on a monthly basis for 1 year. Donor chimerism in CD3+ T cells ranged from 0.05 to 5.1 during the first year after HSCT. We observed a peak of the percentage of regulatory T cells (Tregs). No degree of graft-versus-host disease (GvHD) was observed, and the patient became independent of total parenteral and enteral nutrition. Serial follow-up intestinal biopsies did not show any sign of immune rejection. The patient continued to receive sirolimus to maintain drug concentrations at 6 ng/ml as the only immunosuppression treatment. No signs of rejection were detected after 27 months of follow-up. Patient 2 A 49-year-old woman was diagnosed with chronic kidney failure secondary to rapidly progressive glomerulonephritis. The patient had received 3 previous kidney transplants from deceased donors. A kidney transplant from her sibling was performed in March 2021. Hematopoietic progenitor cells were obtained from mobilized peripheral blood leukapheresis. A NMA conditioning regimen employing total lymphoid irradiation (8 Gy) with antithymocyte globulin (7.5 mg/kg). Two weeks after the kidney transplantation, we infused a graft consisting of 1.27x107/kg CD34+, 4.43x106/kg CD3+CD45RO+, and 5x104/kg CD3+CD45RA+ cells. Controls for hematopoietic chimerism demonstrated the presence of transient mixed hematopoietic chimerism during the first 2 months after SOT of between 0.1% and 40% CD3+ cells. The patient continued on monotherapy with tacrolimus. Immune reconstitution analysis showed a Treg peak. The patient did not have acute rejection, GvHD, viral reactivations or episodes of bacterial infection during the 17 months of follow-up. CONCLUSIONS We describe for the first time the use of non-myeloablative conditioning and a CD45RA− T cell-depleted graft to induce transitory mixed chimerism using both hematopoietic progenitors and a solid organ coming from the same donor, for tolerance induction purposes. The patients continue to progress favorably 17 months or more after SOT, receiving immunosuppressive monotherapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

H. pylori-associated chronic gastritis: status update on the problem

Chronic gastritis is a group of chronic diseases that are morphologically characterized by persistent inflammatory infiltrate and impaired cellular turnover with the development of intestinal metaplasia, atrophy, and epithelial dysplasia in the gastric mucosa. Numerous studies have shown that Helicobacter pylori (H. pylori) infection is the absolutely dominant etiological factor of CG worldwide. Given this fact, the Expert Council of the latest Maastricht VI 2022 consensus recommended that H. pylori is to be treated as a pathogen, which always results in the development of CG. The prevalence of H. pylori-associated CG is about 44.3–48.5%, however 80–90% of cases are asymptomatic. In H. pylori­infected patients with dyspepsia and no other pathology of the gastroduodenal region, which has been confirmed endoscopically, clinical manifestations can be interpreted as part of H. pylori­associated CG if a long-lasting remission of symptoms has been achieved after successful eradication therapy. While patients with persistent dyspeptic symptoms can be considered as patients with functional dyspepsia, despite successful eradication therapy. Advanced endoscopic techniques (narrow band imaging (NBI) endoscopy, high resolution endoscopy, chromoendoscopy, laser confocal endomicroscopy) are precise and reproducible methods for diagnosing precancerous changes in the mucous membrane. However, the diagnosis of CG requires that inflammatory cells have been histologically detected in the lamina propria. The CG therapy aims to reach a persistent relief of dyspeptic symptoms of the disease (if any), as well as resolution of inflammatory processes and prevention of the progression of precancerous changes in the gastric mucosa. The achievement of these goals is primarily determined by the timely diagnosis of H. pylori infection and successful eradication therapy.

Homozygous Missense Epithelial Cell Adhesion Molecule Variant in a Patient with Congenital Tufting Enteropathy and Literature Review.

Congenital diarrheal disorders (CDDs) with genetic etiology are uncommon hereditary intestinal diseases characterized by chronic, life-threatening, intractable watery diarrhea that starts in infancy. CDDs can be mechanistically divided into osmotic and secretory diarrhea. Congenital tufting enteropathy (CTE), also known as intestinal epithelial dysplasia, is a type of secretory CDD. CTE is a rare autosomal recessive enteropathy that presents with intractable neonatal-onset diarrhea, intestinal failure, severe malnutrition, and parenteral nutrition dependence. Villous atrophy of the intestinal epithelium, crypt hyperplasia, and irregularity of surface enterocytes are the specific pathological findings of CTE. The small intestine and occasionally the colonic mucosa include focal epithelial tufts. In 2008, Sivagnanam et al. discovered that mutations in the epithelial cell adhesion molecule (EpCAM, MIM# 185535) were the genetic cause of CTE (MIM# 613217). More than a hundred mutations have been reported to date. Furthermore, mutations in the serine peptidase inhibitor Kunitz type 2 (SPINT2, MIM# 605124) have been linked to syndromic CTE. In this study, we report the case of a 17-month-old male infant with congenital diarrhea. Despite extensive etiological workup, no etiology could be established before admission to our center. The patient died 15 hours after being admitted to our center in a metabolically decompensated state, probably due to a delay in admission and diagnosis. Molecular autopsy with exome sequencing revealed a previously reported homozygous missense variant, c.757G>A, in EpCAM, which was confirmed by histopathological examination.

News in the diagnosis of gastric precancerous lesions

Introduction: Detection and close monitoring of patients with precancerous lesions - chronic atrophic gastritis (GCA), gastric intestinal metaplasia (MIG) and gastric mucosal epithelial dysplasia (DEMG) is a priority to increase early detection and, implicitly, decrease mortality and mortality. by gastric cancer (GC). The aim of the present study is to develop a narrative synthesis of contemporary studies on GCA diagnostic methods. Material and methods: Eligible studies were searched in the PubMed, Hinari, SpringerLink and Scopus (Elsevier) databases during the years 2000-2020. Results: Out of 575 articles addressing the topic of precancerous lesions, 59 articles were qualified representative for the materials published on the topic of this synthesis article. Conclusions: There are two main methodological approaches for GCA evaluation: non-invasive serological examination using gastric function markers and invasive examination, which requires histological analysis of biopsy samples taken during upper digestive endoscopy, the latter being the „gold standard” for diagnosis.

Clinical Recommendations of Russian Gastroenterological Association and RENDO Endoscopic Society on Diagnosis and Treatment of Gastritis and Duodenitis

Aim.The clinical guidelines are intended to supplement specialty decision-making for improved aid quality in patients with gastritis and duodenitis though acknowledging the latest clinical evidence and principles of evidencebased medicine.Key points.Gastritis is an inflammatory disease of stomach mucosa, with a separate definition of acute and chronic gastritis. Chronic gastritis is a cohort of chronic diseases uniting a typical morphology of persistent inflammatory infiltration, impaired cellular renewal with emergent intestinal metaplasia, atrophy and epithelial dysplasia of gastric mucosa. Oesophagogastroduodenoscopy (OGDS) or high-resolution OGDS with magnified or non-magnified virtual chromoendoscopy, including targeted biopsy for atrophy and intestinal metaplasia grading and neoplasia detection, are recommended to verify gastritis and duodenitis, precancer states and/or gastric mucosal changes. All chronic gastritis patients positive for H. рylori should undergo eradication therapy as aetiological and subsidiary for gastric cancer prevention. Chronic gastritis patients with symptoms of dyspepsia (epigastric pain, burning and congestion, early satiety), also combined with functional dyspepsia, are recommended proton pump inhibitors, prokinetics, rebamipide and bismuth tripotassium dicitrate in symptomatic treatment. With focal restricted intestinal metaplasia, follow-up is not required in most cases, mainly when advanced atrophic gastritis is ruled out in high-quality endoscopy with biopsy. However, a familial history of gastric cancer, incomplete intestinal metaplasia and persistent H. pylori infection render endoscopy monitoring with chromoendoscopy and targeted biopsy desirable once in three years. Patients with advanced atrophic gastritis should have high-quality endoscopy every 3 years, and once in 1–2 years if complicated with a familial history of gastric cancer.Conclusion.The recommendations condense current knowledge on the aetiology and pathogenesis of gastritis and duodenitis, as well as laboratory and instrumental diagnostic techniques, main approaches to aetiological H. pylori eradication and treatment of dyspeptic states.

Histopathological Features of the Gastric Mucosa in Patients with Chronic Gastritis and Helicobacter pylori Infection at Pertamina Central Hospital Jakarta

Background: Chronic gastritis is a chronic inflammation of the gastric mucosa, accompanied by changes in mucosal histology with or without Helicobacter pylori infection. Changes in the gastric mucosa include gastric mucosal atrophy, intestinal metaplasia, and epithelial dysplasia. Purposes: This study aims to determine the microscopic appearance of the mucosa in chronic gastritis patients based on standard histopathological criteria, which include gland atrophy, intestinal metaplasia, dysplasia with or without Helicobacter pylori infection at Pertamina Central Hospital Jakarta period 2018 - 2019. Methods: This retrospective study was conducted in a cross-sectional study from March 15 to March 25, 2020. Results: This study reported 303 cases of active chronic gastritis (38.4%) out of 790 total samples that met the inclusion criteria. Microscopic changes of the mucosa were found in the form of atrophy of the mucous glands in 254 cases (32.2%), intestinal metaplasia in 25 cases (3.2%), and epithelial dysplasia cases in 23 cases (2.9%). Conclusion: the proportion of active chronic gastritis patients found in this study was helicobacter pylori infection is more dominantly found in patients with active chronic gastritis than in non-active chronic gastritis. The description of atrophic glands in chronic gastritis patients was more dominant than parameters based on intestinal metaplasia and epithelial dysplasia. It was a finding of intestinal metaplasia compared to all cases showing risk factors that require further clinical observation (follow-up) to detect potential malignancies earlier so that it is necessary to do more preventive action.

Zoledronate Extends Health Span and Survival via the Mevalonate Pathway in a FOXO-dependent Manner.

Over recent decades, increased longevity has not been paralleled by extended health span, resulting in more years spent with multiple diseases in older age. As such, interventions to improve health span are urgently required. Zoledronate (Zol) is a nitrogen-containing bisphosphonate, which inhibits the farnesyl pyrophosphate synthase enzyme, central to the mevalonate pathway. It is already used clinically to prevent fractures in osteoporotic patients, who have been reported to derive unexpected and unexplained survival benefits. Using Drosophila as a model we determined the effects of Zol on life span, parameters of health span (climbing ability and intestinal dysplasia), and the ability to confer resistance to oxidative stress using a combination of genetically manipulated Drosophila strains and Western blotting. Our study shows that Zol extended life span, improved climbing activity, and reduced intestinal epithelial dysplasia and permeability with age. Mechanistic studies showed that Zol conferred resistance to oxidative stress and reduced accumulation of X-ray-induced DNA damage via inhibition of farnesyl pyrophosphate synthase. Moreover, Zol was associated with inhibition of phosphorylated AKT in the mammalian traget of rapamycin pathway downstream of the mevalonate pathway and required dFOXO for its action, both molecules associated with increased longevity. Taken together, our work indicates that Zol, a drug already widely used to prevent osteoporosis and dosed only once a year, modulates important mechanisms of aging. Its repurposing holds great promise as a treatment to improve health span.

Tufting Enteropathy: A Review of Clinical and Histological Presentation, Etiology, Management, and Outcome.

Congenital tufting enteropathy (CTE), also named intestinal epithelial dysplasia, is a rare, autosomal recessive enteropathy with persistent and life-threatening intractable diarrhea early in life. Intractable diarrhea is present independent of breast or formula feeding. Most CTE patients require total parenteral nutrition (TPN), and in severe cases, small bowel transplantation is needed. In the last decade, we have seen remarkable progress in certain aspects, such as the pathogenesis and diagnostic methods of the disease. Rapidly developing molecular analysis techniques have improved the diagnostic methods for CTE and reduced invasive and expensive procedures. Mutations in the gene encoding human epithelial cell adhesion molecule (EpCAM) were identified in the typical form of CTE, which usually exhibits isolated refractory diarrhea. Moreover, the syndromic form of CTE features anal and choanal atresias as well as ophthalmologic signs, which are associated with mutations in the gene encoding Serine Peptidase Inhibitor Kunitz Type 2 (SPINT2). This article reviews CTE disease based on its clinical and histological presentation, etiology and pathogenesis, and management and outcome.

Intestinal epithelial dysplasia

The article presents a clinical case of intestinal epithelial dysplasia (tufting enteropathy), a rare disease which relates to congenital diarrheas, has a particular clinical presentation and is life-threating. The diagnosis was confirmed by histological examination and electronic microscopy of mucous membrane of small intestine. Additional evidence is substantiated for the existence of prenatal markers of intestinal epithelial dysplasia represented as polyhydramnios and intrauterine dilatation of fetal intestinal loops. These symptoms are considered to be a clinical hallmark of sodium and chloride diarrheas and are described in single cases in enteropathy called a microvillus inclusion disease.

Grafting's Function in Patients with Liver Intestinal and Multivisceral Transplantation

Introduction There are few studies of the intestinal graft function in medium and long term. Objectives Assess the functional status of the graft in transplantation patients, once the immediate post-transplant has been overcome. Methodology Patients who received a liver-intestinal or multivisceral transplantation were prospectively evaluated through cross-sectional data collection during a review. Clinical, analytical and functional variables are analyzed. Unstable patients with intercurrent processes were excluded. Results Twenty-six patients were analyzed, 65.38% of them male. 21 with multivisceral graft (80.76%) and 5 liver-intestinal (19.23%). 7 multivisceral grafts were retransplantation (26.92%). The average age at transplantation was 1.73 + / 3.22 years (range: 7 months - 13 years). The average time post-transplant was 3.78 +/- 3.69 years (range 1.5 - 14 years). The indication for transplant was volvulus (19.23%), necrotizing enterocolitis (15.38%), gastroschisis (15.38%), pseudo-obstruction (11.53%), atresia (7.69%) intestinal ischemia (7.69%), epithelial dysplasia (7.69%), MartínezFrías syndrome (3.84%), mitochondrial disease (3.84%) and Hirschsprung's disease (3.84%). 96.15% of patients are autonomous oral-enteral. 1 (3.85%) maintains home parenteral nutrition. 15.38% receive enteral nocturnal nutrition. 3 patients (11.53%) maintain ostomy.Fecal alpha 1-antitrypsin was normal in 92.30% of patients. Fecal elastase was normal at 100%. Faecal fat excretion was normal in 84.61% of patients, only 4 (15.38%) with a moderate steatorrhea. Blood parameters were normal in 100% of patients, including serum citrulline levels with a mean of 37.16 μmol / L (range 21-74). Conclusion 1. Patients with liver-intestinal and multivisceral transplantation have good graft function in medium and long term. 2. Most maintain digestive autonomy. 3. Although in some patients steatorrhea is observed, pancreatic function is normal in 100% of patients with a multivisceral transplantation that includes a pancreatic graft.

Reversal of Intestinal Failure in Children With Tufting Enteropathy Supported With Parenteral Nutrition at Home.

The aim of the study was to review long-term outcome of intestinal epithelial dysplasia (IED)/tufting enteropathy (TE) patients treated with parenteral nutrition (PN) at home managed by an intestinal failure (IF) rehabilitation service. Infants presenting from 1986 to 2010 with IF, and TE histology were retrospectively reviewed for up to 30 years. Data collected included outcome, presentation, nutrition (parenteral/enteral), country of residence, race, EpCAM gene, growth, bone age, and occupation. Thirteen patients (6 boys) in Malta and the UK with TE histology were established on home PN. Survival was 100% for UK children and 92% overall (1 death aged 13 months). Six patients (50% of the surviving 12) weaned off PN. Overall PN requirements reduced with increasing age and <7 infusions/week were needed by 10/12, 83% by 10 years, 6/8, 75% who had reached 15 years, 5/7, 71% who had reached 20, and all 4, 100% >25 years. Two of 12 cases weaned from PN by 10 years, 1 of 8 by 15 years, 3 of 7 by 20 years, and 3 of 4 or 75% >25 years. Seven Maltese patients homozygous for the same EPCAM gene abnormality had a similar outcome to the other cases. Weight, height, bone mineralization, bone age, and insulin-like growth factor-1 (IGF-1) levels were low, but improved with age. Patients achieved educational levels of parents and were employed. IED cases should have >92% chance of long-term survival and >50% chance of enteral autonomy by/in early adult life and 75% by 25 years. Even if PN dependent s/he can gain employment. Patients with IED managed on PN at home by an IF rehabilitation service should avoid intestinal transplant.

Management and prognosis of intestinal epithelial dysplasia

Management and prognosis of intestinal epithelial dysplasia

Matriptase-mediated cleavage of EpCAM destabilizes claudins and dysregulates intestinal epithelial homeostasis.

Congenital tufting enteropathy (CTE) is a severe autosomal recessive human diarrheal disorder with characteristic intestinal epithelial dysplasia. CTE can be caused by mutations in genes encoding EpCAM, a putative adhesion molecule, and HAI-2, a cell surface protease inhibitor. A similar phenotype occurs in mice whose intestinal epithelial cells (IECs) fail to express the tight junction-associated protein claudin-7. EpCAM stabilizes claudin-7 in IECs, and HAI-2 regulates the cell surface serine protease matriptase, a known modifier of intestinal epithelial physiology. Therefore, we hypothesized that HAI-2, matriptase, EpCAM, and claudin-7 were functionally linked. Herein we have demonstrated that active matriptase cleaves EpCAM after Arg80 and that loss of HAI-2 in IECs led to unrestrained matriptase activity and efficient cleavage of EpCAM. Cleavage of EpCAM decreased its ability to associate with claudin-7 and targeted it for internalization and lysosomal degradation in conjunction with claudin-7. CTE-associated HAI-2 mutant proteins exhibited reduced ability to inhibit matriptase and also failed to efficiently stabilize claudin-7 in IECs. These results identify EpCAM as a substrate of matriptase and link HAI-2, matriptase, EpCAM, and claudin-7 in a functionally important pathway that causes disease when it is dysregulated.

Tubular adenoma of the gallblader

Tumors of the gallbladder are rare. Adenomas of the gallbladder is mostly occur as papillary or tubular. Tubular adenomas of the gallbladder occur in middleaged and old people, and it is extremely rare in children. We present 61 year old woman in whom during an ultrasound examination of the abdomen for pain that lasts a long time discovered a chronic inflammation of the gallbladder and slightly polypoid tumor of the gallbladder. Cholecystectomy was performed based on ultrasonographic findings of polyps in the gallbladder. Macroscopic and microscopic established that it is a tubular adenoma type with intestinal epithelial dysplasia, which clearly indicates that it is adenoma with reliable signs of precancer Finding intraoperative cholangiography was normal, and the postoperative course was uneventful.

Abstract LB-306: The Ras exchange factor RasGRP1 opposes proliferative EGFR-SOS1 Ras signals and restricts intestinal epithelial cell growth

Abstract The character of EGFR signals can influence cell fate. Anti-EGFR treatment has been successful as cancer therapy but not in colorectal cancer (CRC) where activating somatic KRAS mutations (KRASMUT) are prevalent. While relevant to CRC, intestinal EGFR signaling is poorly understood, particularly in the context of KRASMUT. Here we show that two distinct Ras nucleotide exchange factors, RasGRP1 and SOS1, lie downstream of the EGFR but act in functional opposition to one another in the context of KRASMUT. RasGRP1 creates a negative feedback loop that limits EGFR-SOS1-Ras signals and restricts CRC growth. Genetic Rasgrp1 depletion from KRasMUT mice exacerbates intestinal epithelial cell growth and dysplasia, leading to a highly serrated colonic epithelium. Furthermore, low RasGRP1 expression in CRC patient specimens correlates with poor clinical outcome. The unexpected inhibitory role of EGFR-RasGRP1 signals in KRASMUT gastrointestinal malignancies reveals an intricacy of EGFR signaling that should be considered for future molecular therapeutics. Citation Format: Philippe Depeille, Linda M. Henricks, Robert van de Ven, Ed Lemmens, Mary Matli, Kevin M. Haigis, David Donner, Robert Warren, Jeroen P. Roose. The Ras exchange factor RasGRP1 opposes proliferative EGFR-SOS1 Ras signals and restricts intestinal epithelial cell growth. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-306. doi:10.1158/1538-7445.AM2014-LB-306

Tufting enteropathy with EpCAM mutation: case report

Tufting enteropathy (TE), also known as intestinal epithelial dysplasia (IED), is a rare congenital enteropathy related to an earlyonset of severe intractable diarrhea due to specific abnormalities of the intestinal epithelium and mutations of the EpCAM gene. TE is characterized by clinical and histological heterogeneity, such as with low or without mononuclear cell infiltration of the lamina propria, and abnormalities of basement membrane. TE can be associated with malformations, other epithelial diseases, or to abnormal enterocytes development and/or differentiation. The authors report a case of a Brazilian child with TE associated with c.556-14A>G mutation in the EpCAM gene (NM_002354.2).

Mucosal Inflammation as a Component of Tufting Enteropathy

Background & Aims: Tufting enteropathy (TE) or intestinal epithelial cell dysplasia is an autosomal recessive inherited condition that is histologically characterized by intestinal tract mucosal changes including villous atrophy, crypt abnormalities and presence of intestinal epithelial cell ‘tufts’. In our TE cohort from the Maltese islands, an inflammatory component was noted in the initial biopsies. The aim of this study was to determine whether inflammation was a significant feature in the small and large bowel mucosal biopsies in this population. Methods: We retrospectively identified and recruited eight patients, including two sets of siblings, with a diagnosis of TE, made during the period 1985-2012 in the Maltese islands and confirmed by negative epithelial cell adhesion molecule (EpCAM) immunohistochemical staining. Clinical, nutritional, endoscopic and histological data were collected from the patient’s medical notes and compared with clinical outcomes. Serial biopsies were taken from infancy and throughout childhood and adulthood as part of routine patient care to monitor disease progression. Results: All eight patients demonstrated a significant chronic inflammatory component in the lamina propria of both their small and large intestine, comprising increased density of plasma cells, eosinophils and lymphocytes. The median follow-up period was 18 years. These inflammatory infiltrates spontaneously resolved completely after a median of 13 years and 15 years respectively. Conclusion: An inflammatory component in both the small and large bowel of the Maltese TE cohort was a significant histological component and thus diagnosis of TE should not be limited to cases with absence of inflammation. Immunogastroenterology 2013; 2:62-67

706 Intestinal Epithelial Dysplasia - A Case Report of a Milder Phenotype

The intractable diarrhea of infancy remains a difficult challenge for the pediatrician.We report a rare case of a five-month-old female infant admitted in “Grigore Alexandrescu” Emergency Children’s Hospital, Bucharest for...

Chronic Diarrhea in Children

Chronic Diarrhea in Children