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Sathiaseelan M, Grammatikopoulos T. Utility of endoscopy in paediatric gastroenterology and hepatology-Review and updates. Dig Liver Dis 2025:S1590-8658(25)00211-7. [PMID: 40024816 DOI: 10.1016/j.dld.2025.01.199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Revised: 01/16/2025] [Accepted: 01/27/2025] [Indexed: 03/04/2025]
Abstract
Paediatric endoscopy has been an integral part of the diagnostic evaluation and management of gastroenterology and hepatology diseases in children. This area of clinical medicine has made meteoric advancements since it was first introduced conserving it's traditional roles of gastroscopy and colonoscopy but broadening significantly it's clinical utility and diagnostic accuracy with new and emerging technology. This article aims to explore and review the current utility and emerging applications of diagnostic and therapeutic endoscopy for the practicing paediatric gastroenterologist and hepatologist.
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Affiliation(s)
- Mohana Sathiaseelan
- Paediatric Liver, GI & Nutrition Centre and MowatLabs, King's College Hospital, London, United Kingdom.
| | - Tassos Grammatikopoulos
- Paediatric Liver, GI & Nutrition Centre and MowatLabs, King's College Hospital, London, United Kingdom; Institute of Liver Studies, School of Immunology & Microbial Sciences, King's College London, London, United Kingdom
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2
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Dreyfuss M, Getz B, Lebwohl B, Ramni O, Underberger D, Ber TI, Steinberg-Koch S, Jenudi Y, Gazit S, Patalon T, Chodick G, Shoenfeld Y, Ben-Tov A. A machine learning tool for early identification of celiac disease autoimmunity. Sci Rep 2024; 14:30760. [PMID: 39730479 DOI: 10.1038/s41598-024-80817-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 11/21/2024] [Indexed: 12/29/2024] Open
Abstract
Identifying which patients should undergo serologic screening for celiac disease (CD) may help diagnose patients who otherwise often experience diagnostic delays or remain undiagnosed. Using anonymized outpatient data from the electronic medical records of Maccabi Healthcare Services, we developed and evaluated five machine learning models to classify patients as at-risk for CD autoimmunity prior to first documented diagnosis or positive serum tissue transglutaminase (tTG-IgA). A train set of highly seropositive (tTG-IgA > 10X ULN) cases (n = 677) with likely CD and controls (n = 176,293) with no evidence of CD autoimmunity was used for model development. Input features included demographic information and commonly available laboratory results. The models were then evaluated for discriminative ability as measured by AUC on a distinct set of highly seropositive cases (n = 153) and controls (n = 41,087). The highest performing model was XGBoost (AUC = 0.86), followed by logistic regression (AUC = 0.85), random forest (AUC = 0.83), multilayer perceptron (AUC = 0.80) and decision tree (AUC = 0.77). Contributing features for the XGBoost model for classifying a patient as at-risk for undiagnosed CD autoimmunity included signs of anemia, transaminitis and decreased high-density lipoprotein. This model's ability to distinguish cases of incident CD autoimmunity from controls shows promise as a potential clinical tool to identify patients with increased risk of having undiagnosed celiac disease in the community, for serologic screening.
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Affiliation(s)
| | | | - Benjamin Lebwohl
- Celiac Disease Center, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
| | - Or Ramni
- Predicta Med Analytics Ltd., Ramat Gan, Israel
| | | | - Tahel Ilan Ber
- Predicta Med Analytics Ltd., Ramat Gan, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- PhaseV, Tel Aviv, Israel
| | | | | | - Sivan Gazit
- Kahn Sagol Maccabi Research & Innovation Center, Maccabi Healthcare Services, Tel Aviv, Israel
| | - Tal Patalon
- Kahn Sagol Maccabi Research & Innovation Center, Maccabi Healthcare Services, Tel Aviv, Israel
| | - Gabriel Chodick
- Kahn Sagol Maccabi Research & Innovation Center, Maccabi Healthcare Services, Tel Aviv, Israel
| | - Yehuda Shoenfeld
- Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Amir Ben-Tov
- Kahn Sagol Maccabi Research & Innovation Center, Maccabi Healthcare Services, Tel Aviv, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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3
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Liu YY, Ye RL, Meng M. Specificity Enhancement of Glutenase Bga1903 toward Celiac Disease-Eliciting Pro-Immunogenic Peptides via Active-Site Modification. Int J Mol Sci 2023; 25:505. [PMID: 38203677 PMCID: PMC10779176 DOI: 10.3390/ijms25010505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 12/28/2023] [Accepted: 12/28/2023] [Indexed: 01/12/2024] Open
Abstract
Celiac disease is an autoimmune disease triggered by oral ingestion of gluten, with certain gluten residues resistant to digestive tract enzymes. Within the duodenum, the remaining peptides incite immunogenic responses, including the generation of autoantibodies and inflammation, leading to irreversible damage. Our previous exploration unveiled a glutenase called Bga1903 derived from the Gram-negative bacterium Burkholderia gladioli. The cleavage pattern of Bga1903 indicates its moderate ability to mitigate the toxicity of pro-immunogenic peptides. The crystal structure of Bga1903, along with the identification of subsites within its active site, was determined. To improve its substrate specificity toward prevalent motifs like QPQ within gluten peptides, the active site of Bga1903 underwent site-directed mutagenesis according to structural insights and enzymatic kinetics. Among the double-site mutants, E380Q/S387L exhibits an approximately 34-fold increase in its specificity constant toward the QPQ sequence, favoring glutamines at the P1 and P3 positions compared to the wild type. The increased specificity of E380Q/S387L not only enhances its ability to break down pro-immunogenic peptides but also positions this enzyme variant as a promising candidate for oral therapy for celiac disease.
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Affiliation(s)
| | | | - Menghsiao Meng
- Graduate Institute of Biotechnology, National Chung Hsing University, 250 Kuo-Kuang Rd., Taichung 40227, Taiwan; (Y.-Y.L.); (R.-L.Y.)
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Molder A, Balaban DV, Molder CC, Jinga M, Robin A. Computer-Based Diagnosis of Celiac Disease by Quantitative Processing of Duodenal Endoscopy Images. Diagnostics (Basel) 2023; 13:2780. [DOI: doi.org/10.3390/diagnostics13172780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2023] Open
Abstract
Celiac disease (CD) is a lifelong chronic autoimmune systemic disease that primarily affects the small bowel of genetically susceptible individuals. The diagnostics of adult CD currently rely on specific serology and the histological assessment of duodenal mucosa on samples taken by upper digestive endoscopy. Because of several pitfalls associated with duodenal biopsy sampling and histopathology, and considering the pediatric no-biopsy diagnostic criteria, a biopsy-avoiding strategy has been proposed for adult CD diagnosis also. Several endoscopic changes have been reported in the duodenum of CD patients, as markers of villous atrophy (VA), with good correlation with serology. In this setting, an opportunity lies in the automated detection of these endoscopic markers, during routine endoscopy examinations, as potential case-finding of unsuspected CD. We collected duodenal endoscopy images from 18 CD newly diagnosed CD patients and 16 non-CD controls and applied machine learning (ML) and deep learning (DL) algorithms on image patches for the detection of VA. Using histology as standard, high diagnostic accuracy was seen for all algorithms tested, with the layered convolutional neural network (CNN) having the best performance, with 99.67% sensitivity and 98.07% positive predictive value. In this pilot study, we provide an accurate algorithm for automated detection of mucosal changes associated with VA in CD patients, compared to normally appearing non-atrophic mucosa in non-CD controls, using histology as a reference.
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Affiliation(s)
- Adriana Molder
- Center of Excellence in Robotics and Autonomous Systems, Military Technical Academy Ferdinand I, 050141 Bucharest, Romania
| | - Daniel Vasile Balaban
- Internal Medicine and Gastroenterology, Central Military Emergency University Hospital, Carol Davila University of Medicine and Pharmacy, 030167 Bucharest, Romania
| | - Cristian-Constantin Molder
- Center of Excellence in Robotics and Autonomous Systems, Military Technical Academy Ferdinand I, 050141 Bucharest, Romania
| | - Mariana Jinga
- Internal Medicine and Gastroenterology, Central Military Emergency University Hospital, Carol Davila University of Medicine and Pharmacy, 030167 Bucharest, Romania
| | - Antonin Robin
- Department of Electronics and Digital Technologies, Polytech Nantes, 44300 Nantes, France
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Molder A, Balaban DV, Molder CC, Jinga M, Robin A. Computer-Based Diagnosis of Celiac Disease by Quantitative Processing of Duodenal Endoscopy Images. Diagnostics (Basel) 2023; 13:2780. [PMID: 37685318 PMCID: PMC10486915 DOI: 10.3390/diagnostics13172780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 08/20/2023] [Accepted: 08/25/2023] [Indexed: 09/10/2023] Open
Abstract
Celiac disease (CD) is a lifelong chronic autoimmune systemic disease that primarily affects the small bowel of genetically susceptible individuals. The diagnostics of adult CD currently rely on specific serology and the histological assessment of duodenal mucosa on samples taken by upper digestive endoscopy. Because of several pitfalls associated with duodenal biopsy sampling and histopathology, and considering the pediatric no-biopsy diagnostic criteria, a biopsy-avoiding strategy has been proposed for adult CD diagnosis also. Several endoscopic changes have been reported in the duodenum of CD patients, as markers of villous atrophy (VA), with good correlation with serology. In this setting, an opportunity lies in the automated detection of these endoscopic markers, during routine endoscopy examinations, as potential case-finding of unsuspected CD. We collected duodenal endoscopy images from 18 CD newly diagnosed CD patients and 16 non-CD controls and applied machine learning (ML) and deep learning (DL) algorithms on image patches for the detection of VA. Using histology as standard, high diagnostic accuracy was seen for all algorithms tested, with the layered convolutional neural network (CNN) having the best performance, with 99.67% sensitivity and 98.07% positive predictive value. In this pilot study, we provide an accurate algorithm for automated detection of mucosal changes associated with VA in CD patients, compared to normally appearing non-atrophic mucosa in non-CD controls, using histology as a reference.
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Affiliation(s)
- Adriana Molder
- Center of Excellence in Robotics and Autonomous Systems, Military Technical Academy Ferdinand I, 050141 Bucharest, Romania
| | - Daniel Vasile Balaban
- Internal Medicine and Gastroenterology, Central Military Emergency University Hospital, Carol Davila University of Medicine and Pharmacy, 030167 Bucharest, Romania
| | - Cristian-Constantin Molder
- Center of Excellence in Robotics and Autonomous Systems, Military Technical Academy Ferdinand I, 050141 Bucharest, Romania
| | - Mariana Jinga
- Internal Medicine and Gastroenterology, Central Military Emergency University Hospital, Carol Davila University of Medicine and Pharmacy, 030167 Bucharest, Romania
| | - Antonin Robin
- Department of Electronics and Digital Technologies, Polytech Nantes, 44300 Nantes, France
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Hue SSS, Ng SB, Wang S, Tan SY. Cellular Origins and Pathogenesis of Gastrointestinal NK- and T-Cell Lymphoproliferative Disorders. Cancers (Basel) 2022; 14:2483. [PMID: 35626087 PMCID: PMC9139583 DOI: 10.3390/cancers14102483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 05/08/2022] [Accepted: 05/13/2022] [Indexed: 11/25/2022] Open
Abstract
The intestinal immune system, which must ensure appropriate immune responses to both pathogens and commensal microflora, comprises innate lymphoid cells and various T-cell subsets, including intra-epithelial lymphocytes (IELs). An example of innate lymphoid cells is natural killer cells, which may be classified into tissue-resident, CD56bright NK-cells that serve a regulatory function and more mature, circulating CD56dim NK-cells with effector cytolytic properties. CD56bright NK-cells in the gastrointestinal tract give rise to indolent NK-cell enteropathy and lymphomatoid gastropathy, as well as the aggressive extranodal NK/T cell lymphoma, the latter following activation by EBV infection and neoplastic transformation. Conventional CD4+ TCRαβ+ and CD8αβ+ TCRαβ+ T-cells are located in the lamina propria and the intraepithelial compartment of intestinal mucosa as type 'a' IELs. They are the putative cells of origin for CD4+ and CD8+ indolent T-cell lymphoproliferative disorders of the gastrointestinal tract and intestinal T-cell lymphoma, NOS. In addition to such conventional T-cells, there are non-conventional T-cells in the intra-epithelial compartment that express CD8αα and innate lymphoid cells that lack TCRs. The central feature of type 'b' IELs is the expression of CD8αα homodimers, seen in monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), which primarily arises from both CD8αα+ TCRαβ+ and CD8αα+ TCRγδ+ IELs. EATL is the other epitheliotropic T-cell lymphoma in the GI tract, a subset of which arises from the expansion and reprograming of intracytoplasmic CD3+ innate lymphoid cells, driven by IL15 and mutations of the JAK-STAT pathway.
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Affiliation(s)
- Susan Swee-Shan Hue
- Department of Pathology, National University Hospital, Singapore 119074, Singapore; (S.S.-S.H.); (S.W.)
| | - Siok-Bian Ng
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore;
- Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
| | - Shi Wang
- Department of Pathology, National University Hospital, Singapore 119074, Singapore; (S.S.-S.H.); (S.W.)
| | - Soo-Yong Tan
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore;
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Ferretti F, Branchi F, Orlando S, Roncoroni L, Barigelletti G, Fabiano S, Vecchi M, Penagini R, Doneda L, Elli L. Effectiveness of Capsule Endoscopy and Double-Balloon Enteroscopy in Suspected Complicated Celiac Disease. Clin Gastroenterol Hepatol 2022; 20:941-949.e3. [PMID: 33189853 DOI: 10.1016/j.cgh.2020.11.010] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 10/31/2020] [Accepted: 11/06/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Complicated celiac disease (CCD) is a rare but severe condition with a poor prognosis. Guidelines recommend use of capsule endoscopy (CE) to explore the small bowel (SB), followed by a double-balloon enteroscopy (DBE) in selected cases with suspected CCD. Our study aimed to evaluate the diagnostic yield (DY) of CE and DBE in identifying and monitoring CCD. METHODS Consecutive suspected CCD patients were enrolled prospectively to undergo CE and/or DBE in the presence of: persistent symptoms despite a correct gluten-free diet (GFD), increased anti-transglutaminase antibodies titer, lack of adherence to the GFD, and CCD monitoring. The DY of CE and DBE were calculated. The incidence of neoplastic complications and mortality were assessed. RESULTS In total, 130 patients (97 women; age, 49 ± 16 y) underwent 151 CEs and 23 DBEs. The DY of CE was 46%. Patients older than age 50 years (at CE examination or at CD diagnosis) with a CD duration shorter than 5 years were at higher risk of positive CE (relative risk, 1.6 and 1.7 in case of enrollement or CD diagnosis after 50 years of age, and 1.5 in case of short CD duration; P < .05) than their counterparts. Up to 40% of SB lesions were unreachable by upper endoscopy. At the end of the diagnostic work-up, 25 patients with premalignant/malignant lesions were identified: 12 type 1 refractory CD (RCD-1), 7 type 2 RCD (RCD-2), and 6 enteropathy-associated T-cell lymphoma (EATL). Six patients died: 2 patients with RCD-2 and 4 patients with EATL. CONCLUSIONS In case of suspected CCD, CE should be the first-line approach to detect complications and to identify patients deserving DBE. Older and symptomatic patients with suspected CCD deserve a careful evaluation of the SB, especially during the first years after diagnosis.
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Affiliation(s)
- Francesca Ferretti
- Center for the Prevention and Diagnosis of Celiac Disease, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gastroenterology and Endoscopy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Federica Branchi
- Center for the Prevention and Diagnosis of Celiac Disease, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gastroenterology and Endoscopy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Stefania Orlando
- Center for the Prevention and Diagnosis of Celiac Disease, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gastroenterology and Endoscopy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Leda Roncoroni
- Center for the Prevention and Diagnosis of Celiac Disease, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Biomedical, Surgical and Dental Sciences, Milan, Italy
| | - Giulio Barigelletti
- Cancer Registry Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori Milano, Milan Italy
| | - Sabrina Fabiano
- Cancer Registry Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori Milano, Milan Italy
| | - Maurizio Vecchi
- Center for the Prevention and Diagnosis of Celiac Disease, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gastroenterology and Endoscopy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Roberto Penagini
- Gastroenterology and Endoscopy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Luisa Doneda
- Department of Biomedical, Surgical and Dental Sciences, Milan, Italy
| | - Luca Elli
- Center for the Prevention and Diagnosis of Celiac Disease, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gastroenterology and Endoscopy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
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Calado J, Verdelho Machado M. Celiac Disease Revisited. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2022; 29:111-124. [PMID: 35497669 PMCID: PMC8995660 DOI: 10.1159/000514716] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Accepted: 01/08/2021] [Indexed: 08/30/2023]
Abstract
Celiac disease (CD) is a systemic disease triggered by gluten ingestion in genetically predisposed individuals. It manifests primarily as an autoimmune enteropathy associated with specific circulating autoantibodies and a human leukocyte antigen haplotype (HLA-DQ2 or HLA-DQ8). It afflicts roughly 1% of the population, though the majority of patients remain undiagnosed. Diarrhea and malabsorption are classic manifestations of CD; however, both children and adults can be paucisymptomatic and present extraintestinal manifestations such as anemia, osteoporosis, and abnormal liver tests. CD screening is not recommended for the general population, and it should be focused on high-risk groups. CD diagnosis is challenging and relies on serological tests, duodenal histology, and genetic testing. Particularly difficult presentations to manage are seronegative patients, seropositive patients without villus atrophy, and patients who have started a gluten-free diet before the diagnostic workup. The only proven treatment is a lifelong gluten-free diet. We present an in-depth review on the physiopathology and management of CD, with a particular emphasis on diagnostic challenges.
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Affiliation(s)
- João Calado
- Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Mariana Verdelho Machado
- Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
- Hospital de Vila Franca de Xira, Vila Franca de Xira, Portugal
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9
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Pal P, Singh AP, Kanuri ND, Banerjee R. Electronic chromo-endoscopy: technical details and a clinical perspective. Transl Gastroenterol Hepatol 2022; 7:6. [PMID: 35243115 PMCID: PMC8826039 DOI: 10.21037/tgh-19-373] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Accepted: 05/12/2020] [Indexed: 08/13/2023] Open
Abstract
Precise endoscopic assessment is necessary to detect neoplastic changes in an early stage. Electronic or virtual chromo-endoscopy (ECE) is an alternative to conventional dye-based chromo-endoscopy which markedly improves capillary pattern and hence can detect micro-vessel morphological changes of early neoplasia to target biopsies and aid in diagnosis. The clinical significance increased after the advent of endoscopic treatment modalities like ESD/EMR which requires precise delineation of extent and depth of lesion. Most of the studies have used narrow-band imaging (NBI) (Olympus Medical Systems Tokyo, Japan), although data from i-SCAN (PENTAX Endoscopy, Tokyo, Japan) and flexible spectral imaging color enhancement (FICE) (Fujinon, Fujifilm Medical Co, Saitama, Japan) are emerging. Electronic chromo-endoscopy is convenient compared to dye-based chromo-endoscopy in the sense that it is available at the push of a button in endoscope and reduces procedure time substantially with comparable efficacy. Scope of this review is to discuss available electronic chromo-endoscopy modalities and their role in the diagnosis, surveillance, and management of early GI neoplasia.
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Affiliation(s)
- Partha Pal
- Department of Medical Gastroenterology, AIG hospitals, Hyderabad, India
| | | | - Navya D Kanuri
- Department of Medical Gastroenterology, AIG hospitals, Hyderabad, India
| | - Rupa Banerjee
- Department of Medical Gastroenterology, AIG hospitals, Hyderabad, India
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10
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Sinha SK, Berry N, Muktesh G, Siddappa P, Basha J, Prasad K, Appasani S, Ashat M, Vaiphei K, Singh K, Kochhar R. Utility of narrow band imaging in predicting histology in celiac disease. Indian J Gastroenterol 2020; 39:370-376. [PMID: 32705418 DOI: 10.1007/s12664-020-01030-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Accepted: 03/24/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Narrow band imaging (NBI) with magnification better visualizes the duodenal microsurface and mucosal vascularity. NBI delineates villous atrophy better than conventional white light endoscopy. AIMS This study was conducted to evaluate the diagnostic accuracy of narrow band imaging with magnification (NBI-ME) in celiac disease (CD). METHODS In this prospective study, consecutive patients of suspected CD and controls were subjected to tissue transglutaminase antibody test and endoscopic evaluation initially with white light followed by NBI-ME, and biopsies were taken from duodenum. Duodenal villous patterns on NBI were interpreted as normal, blunted distorted, and absent. Severity of villous atrophy was reported according to the modified Marsh criteria. RESULTS One hundred and twenty-two patients (mean age of 27.53 ± 13.37 years and a male to female ratio of 1:1.26) and 40 controls were studied. The sensitivity and specificity of NBI-ME in predicting villous atrophy were found to be 95.54% and 90%, respectively. The specificity and negative predictive value of NBI-ME in predicting villous atrophy amongst controls was 100% and 97.5%, respectively. Abnormal findings (blunted and absent villous patterns) combined with elevated transglutaminase antibody (> 5-fold) were found to have high accuracy in predicting villous atrophy. CONCLUSION NBI with magnification has high sensitivity and specificity in predicting villous atrophy in patients with celiac disease.
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Affiliation(s)
- Saroj Kant Sinha
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India
| | - Neha Berry
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India
| | - Gaurav Muktesh
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India
| | - Pradeep Siddappa
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India
| | - Jahangeer Basha
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India
| | - Kaushal Prasad
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India
| | - Sreekanth Appasani
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India
| | - Munish Ashat
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India
| | - Kim Vaiphei
- Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India
| | - Kartar Singh
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India
| | - Rakesh Kochhar
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India.
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11
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Sahyouni A, Ibrahim A, Ibrahim A. Diagnostic values of duodenal endoscopic markers in paediatric coeliac patients. Arab J Gastroenterol 2020; 21:28-31. [PMID: 32086001 DOI: 10.1016/j.ajg.2020.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Revised: 12/15/2019] [Accepted: 01/26/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND STUDY AIMS The recognition of suggestive endoscopic markers in the duodenum during open access endoscopy can help identifying patients who are likely to develop coeliac disease (CD). This study aims to determine the diagnostic accuracy of duodenal endoscopic markers for the diagnosis of CD. PATIENTS AND METHODS All children (0-15 years) who underwent oesophagogastroduodenoscopy (EGD) for any reason suggestive of CD at the paediatric department of Al-Assad University Hospital in Latakia, Syria during a 4-year period (from January 2010 to December 2013) were retrospectively included, in the study; this yielded a consecutive cohort without selection bias. The relevant data were obtained from the patients' files. Four duodenal endoscopic markers, including scalloping, reduction of duodenal folds, nodular mucosal pattern, and scattered white spots, were evaluated. RESULTS During the study period, 504 children underwent EGD of whom 123 (24.4%) were ultimately diagnosed with CD. At least one marker was observed in 200/504 children (39.6%) and the diagnostic values were as follows: Sensitivity (91%), specificity (76%), positive predictive value (56%), and negative predictive value (97%). Scalloping had the highest sensitivity and specificity of 89% and 96%, respectively. CONCLUSION Careful examination of the second and third parts of the duodenum during endoscopy can be helpful in identifying CD. Scalloping is the most common endoscopic marker, and the high NPV values of endoscopic markers should be interpreted cautiously, as the diagnosis of CD can be missed.
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Affiliation(s)
| | - Ali Ibrahim
- Department of Paediatrics, Faculty of Medicine, Tishreen University, Latakia, Syria
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Affiliation(s)
- Jihong Min
- Andrew and Peggy Cherng Department of Medical EngineeringDivision of Engineering and Applied ScienceCalifornia Institute of Technology Pasadena CA 91125 USA
| | - Yiran Yang
- Andrew and Peggy Cherng Department of Medical EngineeringDivision of Engineering and Applied ScienceCalifornia Institute of Technology Pasadena CA 91125 USA
| | - Zhiguang Wu
- Andrew and Peggy Cherng Department of Medical EngineeringDivision of Engineering and Applied ScienceCalifornia Institute of Technology Pasadena CA 91125 USA
| | - Wei Gao
- Andrew and Peggy Cherng Department of Medical EngineeringDivision of Engineering and Applied ScienceCalifornia Institute of Technology Pasadena CA 91125 USA
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Faye AS, Lebwohl B. Celiac Disease: Diagnosis, Screening, and Prognosis. EVIDENCE‐BASED GASTROENTEROLOGY AND HEPATOLOGY 4E 2019:139-149. [DOI: 10.1002/9781119211419.ch9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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14
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Chetcuti Zammit S, Sanders DS, Sidhu R. A comprehensive review on the utility of capsule endoscopy in coeliac disease: From computational analysis to the bedside. Comput Biol Med 2018; 102:300-314. [PMID: 29980284 DOI: 10.1016/j.compbiomed.2018.06.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 06/23/2018] [Accepted: 06/24/2018] [Indexed: 11/29/2022]
Abstract
Small bowel capsule endoscopy (SBCE) can identify macroscopic changes of coeliac disease and assess the extent of disease in the small bowel beyond the duodenum. SBCE has a good sensitivity for the detection of coeliac disease in comparison to histology owing to several ideal features such as a high magnification. It also plays a useful role in detecting complications in patients with refractory coeliac disease. Several studies have been carried out on transforming images obtained from small bowel capsule endoscopy to enable the automated detection of features related to coeliac disease. This review discusses the current roles played by small bowel capsule endoscopy in coeliac disease. It identifies future potential roles of this technique and describes in great detail the role of computational analysis in the detection of coeliac disease and how it can be adapted to current available technology.
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Affiliation(s)
- Stefania Chetcuti Zammit
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, UK.
| | - David S Sanders
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, UK
| | - Reena Sidhu
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, UK
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Chetcuti Zammit S, Sanders DS, Sidhu R. Capsule endoscopy for patients with coeliac disease. Expert Rev Gastroenterol Hepatol 2018; 12:779-790. [PMID: 29886766 DOI: 10.1080/17474124.2018.1487289] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Coeliac disease is an autoimmune mediated condition in response to gluten. A combination of innate and adaptive immune responses results in villous shortening in the small bowel (SB) that can be morphologically picked up on capsule endoscopy. It is the only imaging modality that can provide mucosal views of the entire SB, while histology is generally limited to the proximal SB. Radiological modalities are not designed to pick up changes in villous morphology. Areas covered: In this review, we provide a comprehensive analysis on the justified use of small bowel capsule endoscopy (SBCE) in the assessment of patients with coeliac disease; compare SBCE to histology, serology, and symptomatology; and provide an overview on automated quantitative analysis for the detection of coeliac disease. We also provide insight into future work on SBCE in relation to coeliac disease. Expert commentary: SBCE has opened up new avenues for the diagnosis and monitoring of patients with coeliac disease. However, larger studies with new and established coeliac disease patients and with greater emphasis on morphological features on SBCE are required to better define the role of SBCE in the setting of coeliac disease.
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Affiliation(s)
| | - David S Sanders
- a Gastroenterology Department , Sheffield Teaching Hospitals , Sheffield , UK
| | - Reena Sidhu
- a Gastroenterology Department , Sheffield Teaching Hospitals , Sheffield , UK
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Position paper: The potential role of optical biopsy in the study and diagnosis of environmental enteric dysfunction. Nat Rev Gastroenterol Hepatol 2017; 14:727-738. [PMID: 29139480 DOI: 10.1038/nrgastro.2017.147] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Environmental enteric dysfunction (EED) is a disease of the small intestine affecting children and adults in low and middle income countries. Arising as a consequence of repeated infections, gut inflammation results in impaired intestinal absorptive and barrier function, leading to poor nutrient uptake and ultimately to stunting and other developmental limitations. Progress towards new biomarkers and interventions for EED is hampered by the practical and ethical difficulties of cross-validation with the gold standard of biopsy and histology. Optical biopsy techniques - which can provide minimally invasive or noninvasive alternatives to biopsy - could offer other routes to validation and could potentially be used as point-of-care tests among the general population. This Consensus Statement identifies and reviews the most promising candidate optical biopsy technologies for applications in EED, critically assesses them against criteria identified for successful deployment in developing world settings, and proposes further lines of enquiry. Importantly, many of the techniques discussed could also be adapted to monitor the impaired intestinal barrier in other settings such as IBD, autoimmune enteropathies, coeliac disease, graft-versus-host disease, small intestinal transplantation or critical care.
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Shamban L, Sorser S, Naydin S, Lebwohl B, Shukr M, Wiemann C, Yevsyukov D, Piper MH, Warren B, Green PHR. Factors associated with number of duodenal samples obtained in suspected celiac disease. Endosc Int Open 2017; 5:E1220-E1228. [PMID: 29218313 PMCID: PMC5718903 DOI: 10.1055/s-0043-120522] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Accepted: 06/26/2017] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND AND STUDY AIMS Many people with celiac disease are undiagnosed and there is evidence that insufficient duodenal samples may contribute to underdiagnosis. The aims of this study were to investigate whether more samples leads to a greater likelihood of a diagnosis of celiac disease and to elucidate factors that influence the number of samples collected. PATIENTS AND METHODS We identified patients from two community hospitals who were undergoing duodenal biopsy for indications (as identified by International Classification of Diseases code) compatible with possible celiac disease. Three cohorts were evaluated: no celiac disease (NCD, normal villi), celiac disease (villous atrophy, Marsh score 3), and possible celiac disease (PCD, Marsh score < 3). Endoscopic features, indication, setting, trainee presence, and patient demographic details were evaluated for their role in sample collection. RESULTS 5997 patients met the inclusion criteria. Patients with a final diagnosis of celiac disease had a median of 4 specimens collected. The percentage of patients diagnosed with celiac disease with one sample was 0.3 % compared with 12.8 % of those with six samples ( P = 0.001). Patient factors that positively correlated with the number of samples collected were endoscopic features, demographic details, and indication ( P = 0.001). Endoscopist factors that positively correlated with the number of samples collected were absence of a trainee, pediatric gastroenterologist, and outpatient setting ( P < 0.001). CONCLUSIONS Histological diagnosis of celiac disease significantly increased with six samples. Multiple factors influenced whether adequate biopsies were taken. Adherence to guidelines may increase the diagnosis rate of celiac disease.
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Affiliation(s)
- Leonid Shamban
- Gastroenterology, Genesys Regional Medical Center, Grand Blanc, Michigan, United States,Corresponding author Leonid Shamban, DO GastroenterologyGenesys Regional Medical CenterOne Genesys ParkwayGrand BlancMichigan 48439-1477United States+1-810-606-5990
| | - Serge Sorser
- Gastroenterology, Providence-Providence Park Hospital, Novi, Michigan, United States
| | - Stan Naydin
- Internal Medicine, Drexel University, Philadelphia, Pennsylvania, United States
| | - Benjamin Lebwohl
- Clinical Medicine, Columbia University, New York, New York, United States
| | - Mousa Shukr
- Internal Medicine, Providence-Providence Park Hospital, Southfield, Michigan, United States
| | - Charlotte Wiemann
- Internal Medicine, Providence-Providence Park Hospital, Southfield, Michigan, United States
| | - Daniel Yevsyukov
- Division of Solid Organ Transplant, University of Minnesota Medical School Twin Cities, Minneapolis, Minnesota, United States
| | - Michael H. Piper
- Gastroenterology, Providence-Providence Park, Southfield, Michigan, United States
| | - Bradley Warren
- Gastroenterology, Providence-Providence Park, Southfield, Michigan, United States
| | - Peter H. R. Green
- Clinical Medicine, Columbia University, New York, New York, United States
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Efthymakis K, Milano A, Laterza F, Serio M, Neri M. Iron deficiency anemia despite effective gluten-free diet in celiac disease: Diagnostic role of small bowel capsule endoscopy. Dig Liver Dis 2017; 49:412-416. [PMID: 28065527 DOI: 10.1016/j.dld.2016.12.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Revised: 12/01/2016] [Accepted: 12/05/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIM Iron deficiency anemia (IDA) is associated with celiac disease (CD). Although gluten-free diet (GFD) is an efficient treatment for CD, IDA remains an occasional finding during follow-up and correlates to inadequate gluten exclusion. Little is known regarding persistent IDA despite effective GFD. We aimed to evaluate the role of small bowel capsule endoscopy (SBCE) in this setting. METHODS We prospectively included consecutive patients undergoing GFD for ≥24 months with persistent concomitant IDA. Patients were assessed serologically and, if negative, underwent endoscopic evaluation. RESULTS Twenty-six patients underwent esophago-gastro-duodenoscopy (EGD), colonoscopy and SBCE. Altogether, 11 patients resulted positive. EGD showed mucosal lesions in 7: erosive gastritis (n=3), erosive duodenitis (n=1), active CD (n=3). Colonoscopy showed hemorrhoids in 2. SBCE was positive in 6 cases: erosive jejunitis (n=3, 1 eventually diagnosed as refractory CD, 2 as Crohn's disease), angiodysplasias (n=2), lymphangectasia (n=1). Some overlap was observed between procedures, since in 4 subjects EGD and SBCE produced significant findings. However, in 3 cases SBCE documented severe disease, not found at EGD. Hypoalbuminemia was significantly associated with a positive SBCE outcome (p<0.01). CONCLUSION SBCE yielded significant findings in 23% of celiacs with persistent IDA despite adequate GFD. These were associated to hypoalbuminemia, indicating their occurrence at more severe stages of the disease.
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Affiliation(s)
- Konstantinos Efthymakis
- Department of Medicine and Ageing Sciences and Center for Excellence on Ageing and Translational Medicine (CeSI-MeT), "G. D'Annunzio" University and Foundation, Chieti, Italy
| | - Angelo Milano
- Department of Medicine and Ageing Sciences and Center for Excellence on Ageing and Translational Medicine (CeSI-MeT), "G. D'Annunzio" University and Foundation, Chieti, Italy
| | - Francesco Laterza
- Department of Medicine and Ageing Sciences and Center for Excellence on Ageing and Translational Medicine (CeSI-MeT), "G. D'Annunzio" University and Foundation, Chieti, Italy
| | - Mariaelena Serio
- Department of Medicine and Ageing Sciences and Center for Excellence on Ageing and Translational Medicine (CeSI-MeT), "G. D'Annunzio" University and Foundation, Chieti, Italy
| | - Matteo Neri
- Department of Medicine and Ageing Sciences and Center for Excellence on Ageing and Translational Medicine (CeSI-MeT), "G. D'Annunzio" University and Foundation, Chieti, Italy.
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Ciaccio EJ, Bhagat G, Lewis SK, Green PH. Recommendations to quantify villous atrophy in video capsule endoscopy images of celiac disease patients. World J Gastrointest Endosc 2016; 8:653-662. [PMID: 27803772 PMCID: PMC5067472 DOI: 10.4253/wjge.v8.i18.653] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2016] [Revised: 06/10/2016] [Accepted: 08/16/2016] [Indexed: 02/05/2023] Open
Abstract
AIM To quantify the presence of villous atrophy in endoscopic images for improved automation.
METHODS There are two main categories of quantitative descriptors helpful to detect villous atrophy: (1) Statistical and (2) Syntactic. Statistical descriptors measure the small intestinal substrate in endoscope-acquired images based on mathematical methods. Texture is the most commonly used statistical descriptor to quantify villous atrophy. Syntactic descriptors comprise a syntax, or set of rules, for analyzing and parsing the substrate into a set of objects with boundaries. The syntax is designed to identify and distinguish three-dimensional structures based on their shape.
RESULTS The variance texture statistical descriptor is useful to describe the average variability in image gray level representing villous atrophy, but does not determine the range in variability and the spatial relationships between regions. Improved textural descriptors will incorporate these factors, so that areas with variability gradients and regions that are orientation dependent can be distinguished. The protrusion syntactic descriptor is useful to detect three-dimensional architectural components, but is limited to identifying objects of a certain shape. Improvement in this descriptor will require incorporating flexibility to the prototypical template, so that protrusions of any shape can be detected, measured, and distinguished.
CONCLUSION Improved quantitative descriptors of villous atrophy are being developed, which will be useful in detecting subtle, varying patterns of villous atrophy in the small intestinal mucosa of suspected and known celiac disease patients.
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Broide E, Matalon S, Kriger-Sharabi O, Richter V, Shirin H, Leshno M. Cost effectiveness of routine duodenal biopsies in iron deficiency anemia. World J Gastroenterol 2016; 22:7813-7823. [PMID: 27678365 PMCID: PMC5016382 DOI: 10.3748/wjg.v22.i34.7813] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2016] [Revised: 07/11/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the cost effectiveness of routine small bowel biopsies (SBBs) in patients with iron deficiency anemia (IDA) independent of their celiac disease (CD) serology test results.
METHODS We used a state transition Markov model. Two strategies were compared: routine SBBs during esophagogastroduodenoscopy (EGD) in all patients with IDA regardless their celiac serology status (strategy A) vs SBBs only in IDA patients with positive serology (strategy B). The main outcomes were quality adjusted life years (QALY), average cost and the incremental cost effectiveness ratio (ICER). One way sensitivity analysis was performed on all variables and two way sensitivity analysis on selected variables were done. In order to validate the results, a Monte Carlo simulation of 100 sample trials with 10, and an acceptability curve were performed.
RESULTS Strategy A of routine SBBs yielded 19.888 QALYs with a cost of $218.10 compared to 19.887 QALYs and $234.17 in strategy B. In terms of cost-effectiveness, strategy A was the dominant strategy, as long as the cost of SBBs stayed less than $67. In addition, the ICER of strategy A was preferable, providing the cost of biopsy stays under $77. Monte Carlo simulation demonstrated that strategy A yielded the same QALY but with lower costs than strategy B.
CONCLUSION Our model suggests that EGD with routine SBBs is a cost-effective approach with improved QALYs in patients with IDA when the prevalence of CD is 5% or greater. SBBs should be a routine screening tool for CD among patients with IDA, regardless of their celiac antibody status.
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Bonatto MW, Kotze L, Orlandoski M, Tsuchyia R, de Carvalho CA, Lima D, Kurachi G, Orso IR, Kotze L. Endoscopic evaluation of celiac disease severity and its correlation with histopathological aspects of the duodenal mucosa. Endosc Int Open 2016; 4:E767-77. [PMID: 27556094 PMCID: PMC4993899 DOI: 10.1055/s-0042-108190] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2015] [Accepted: 04/27/2016] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND AND STUDY AIMS Celiac disease (CD) is a chronic systemic autoimmune disorder affecting genetically predisposed individuals, triggered and maintained by the ingestion of gluten. Triggered and maintained by the ingestion of gluten, celiac disease is a chronic systemic autoimmune disorder affecting genetically predisposed individuals. Persistent related inflammation of the duodenal mucosa causes atrophy architecture detectable on esophagogastroduodenoscopy (EGD) and histopathology. We investigated the association between endoscopic features and histopathological findings (Marsh) for duodenal mucosa in celiac disease patients and propose an endoscopic classification of severity. PATIENTS AND METHODS Between January 2000 and March 2010, an electronic database containing 34,540 EDGs of patients aged > 14 years was searched for cases of CD. Out of 109 cases, 85 met the inclusion criteria: conventional EGD combined with chromoendoscopy, zoom and biopsy. EGD types 0, I and II corresponds to Marsh grades 0, 1 and 2, respectively, while EGD type III corresponds to Marsh grade 3 and 4. RESULTS Five patients (5.8 %) were EGD I but not Marsh grade 1; 25 patients (29.4 %) were EGD II, 4 of whom (16 %) were classified as Marsh grade 2; and 55 patients (64.7 %) were EGD III, 51 (92.7 %) of whom were classified as Marsh grades 3 and 4. The Spearman correlation coefficient (r = 0.33) revealed a significant association between the methods (P = 0.002). CONCLUSIONS Changes in the duodenal mucosa detected on EGD were significantly and positively associated with histopathologic findings. The use of chromoendoscopy in addition to conventional EGD enhances changes in the duodenal mucosa and permits diagnosis of CD, even in routine examinations. The proposed endoscopic classification is practical and easily reproducible and provides valuable information regarding disease extension.
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Affiliation(s)
- Mauro W. Bonatto
- Gastroclínica Cascavel, Gastroenterology Center, Parana, Brazil,Assis Gurgacz University Center – School of Medicine, Cascavel, Brazil
| | - Luiz Kotze
- Pontifícia Universidade Católica do Paraná, Curitiba, Brazil
| | | | | | | | - Doryane Lima
- Gastroclínica Cascavel, Gastroenterology Center, Parana, Brazil,Assis Gurgacz University Center – School of Medicine, Cascavel, Brazil
| | - Gustavo Kurachi
- Gastroclínica Cascavel, Gastroenterology Center, Parana, Brazil,Assis Gurgacz University Center – School of Medicine, Cascavel, Brazil
| | - Ivan R.B. Orso
- Gastroclínica Cascavel, Gastroenterology Center, Parana, Brazil,Assis Gurgacz University Center – School of Medicine, Cascavel, Brazil
| | - Lorete Kotze
- Pontifícia Universidade Católica do Paraná, Curitiba, Brazil
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Kurppa K, Taavela J, Saavalainen P, Kaukinen K, Lindfors K. Novel diagnostic techniques for celiac disease. Expert Rev Gastroenterol Hepatol 2016; 10:795-805. [PMID: 26838683 DOI: 10.1586/17474124.2016.1148599] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The diagnosis of celiac disease has long been based on the demonstration of gluten-induced small-bowel mucosal damage. However, due to the constantly increasing disease prevalence and limitations in the histology-based criteria there is a pressure towards more serology-based diagnostics. The serological tools are being improved and new non-invasive methods are being developed, but the constantly refined endoscopic and histologic techniques may still prove helpful. Moreover, growing understanding of the disease pathogenesis has led researchers to suggest completely novel approaches to celiac disease diagnostics regardless of disease activity. In this review, we will elucidate the most recent development and possible future innovations in the diagnostic techniques for celiac disease.
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Affiliation(s)
- Kalle Kurppa
- a Tampere Centre for Child Health Research , University of Tampere and Tampere University Hospital , Tampere , Finland
| | - Juha Taavela
- a Tampere Centre for Child Health Research , University of Tampere and Tampere University Hospital , Tampere , Finland
| | - Päivi Saavalainen
- b Molecular Genetics of Immunological Diseases Group , University of Helsinki , Helsinki , Finland
| | - Katri Kaukinen
- c Department of Internal Medicine , Tampere University Hospital , Tampere , Finland.,d School of Medicine , University of Tampere , Tampere , Finland
| | - Katri Lindfors
- a Tampere Centre for Child Health Research , University of Tampere and Tampere University Hospital , Tampere , Finland
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Cammarota G, Ianiro G. Endoscopic evaluation of celiac disease. Endosc Int Open 2016; 4:E547-8. [PMID: 27227113 PMCID: PMC4874789 DOI: 10.1055/s-0042-105435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Accepted: 03/14/2016] [Indexed: 10/25/2022] Open
Affiliation(s)
- Giovanni Cammarota
- Internal Medicine, Gastroenterology and Liver Unit; “A. Gemelli” University Hospital, Rome, Italy ,Corresponding author Prof. Giovanni Cammarota, MD Gemelli University HospitalInternal Medicine, Gastroenterology and Liver UnitLargo A. Gemelli8, 00168 – RomaItalia+39-06-35502775
| | - Gianluca Ianiro
- Internal Medicine, Gastroenterology and Liver Unit; “A. Gemelli” University Hospital, Rome, Italy
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Prior Misdiagnosis of Celiac Disease Is Common Among Patients Referred to a Tertiary Care Center: A Prospective Cohort Study. Clin Transl Gastroenterol 2016; 7:e139. [PMID: 26821194 PMCID: PMC4737868 DOI: 10.1038/ctg.2015.48] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 09/16/2015] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVES Interest of patients and physicians in celiac disease is growing worldwide, but without a corresponding increase in the awareness of the disease. Many patients are diagnosed as celiacs even without completing the whole diagnostic process, with consequent risk of misdiagnosis and delay in the evaluation of other diseases. The objective of this study was to assess the rates of prior celiac disease misdiagnosis among patients referred to a tertiary care center. METHODS From June 2013 to December 2014, we prospectively recruited patients referred for the first time to our Celiac Disease Center. Patients with a previous diagnosis of celiac disease underwent a diagnostic revaluation by second reading of duodenal tissue slides, dosage of specific antibodies, and/or duodenal biopsy sampling; HLA status was investigated in pertinent cases. RESULTS A total of 198 subjects were recruited. Of these, 91 "naïve" patients (46%) started the diagnostic screening for celiac disease; 58 of them (64-29% of the whole sample) were diagnosed as celiacs. The remaining 107 patients (54%) came with a previous diagnosis of celiac disease: of these, 52 (49-26% of the whole sample) presented with confirmed diagnosis of celiac disease, whereas 55 (51-28% of the whole sample) underwent diagnostic revaluation. After the reassessment, diagnosis was rejected in 43 cases (78-22% of the whole sample) and confirmed in the remaining 12 (22-6% of the whole sample). Overall, diagnosis was confirmed in only 64 of the 107 subjects with a previous diagnosis (60-32% of the whole sample). Diagnosis of celiac disease was more frequently confirmed in "naïve" patients compared those with a questionable previous diagnosis (64% vs. 22%; P<0.0001). CONCLUSIONS A considerable number of patients referred to a tertiary care center are inaccurately diagnosed with celiac disease. Although we cannot exclude that uncertain diagnosis was a reason for the referral, we suggest greater adherence to guidelines to minimize the burden of celiac disease misdiagnosis.
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Dutta AK, Chacko A. Emerging role of narrow band imaging in duodenum. World J Gastrointest Endosc 2015; 7:1216-1221. [PMID: 26566428 PMCID: PMC4639743 DOI: 10.4253/wjge.v7.i16.1216] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Revised: 08/20/2015] [Accepted: 09/30/2015] [Indexed: 02/05/2023] Open
Abstract
Endoscopy using magnification narrow band imaging (mNBI) allows detailed assessment of mucosal surface and vascular pattern. This may help in better identification and prediction of the nature of the lesion. The role of this technology in duodenum is still evolving. Studies have shown that mNBI has high accuracy in predicting villous atrophy in the duodenum. Limited data suggests that this technique can provide additional information on duodenal polyps, nodules and ampullary tumour which can help guide their management. In this paper we describe the technique for duodenal assessment using NBI and review the existing literature evaluating its role in diagnosis of various duodenal pathologies.
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Balaban DV, Popp A, Vasilescu F, Haidautu D, Purcarea RM, Jinga M. Diagnostic yield of endoscopic markers for celiac disease. J Med Life 2015; 8:452-457. [PMID: 26664469 PMCID: PMC4656951 DOI: pmid/26664469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Accepted: 09/30/2015] [Indexed: 02/07/2023] Open
Abstract
RATIONALE In the setting of open access endoscopy, the recognition of suggestive endoscopic features in the duodenum can select patients with probability of celiac disease (CD). This could add to the current efforts to increase the diagnostic rate of this disease. AIM The aim of this study was to evaluate the diagnostic accuracy of these markers for CD in an adult population undergoing endoscopy, without a prior serological testing. METHODS AND RESULTS Over a period of 3 years, between June 2012 and 2015, all the patients who underwent upper gastrointestinal endoscopy and presented one or more of the endoscopic markers consistent with CD, or those suspected for CD, irrespective of the presence of these markers, were included. Sensitivity, specificity, positive and negative predictive values were calculated for these markers in CD diagnosis. Among the 182 patients, 56.04% were females, with a mean age of 47.6 ± 13.9 years. 20/182 (10.99%) had a final diagnosis of CD. The presence of any endoscopic marker had a high sensitivity (95%) and a negative predictive value (98.41%). Bulb atrophy and reduced folds in the descending duodenum had a low diagnostic accuracy, while scalloping, mosaic pattern and fissures were highly specific for CD (98.77%, 99.38% and 98.77%) and their presence greatly increased the probability of CD, with a positive likelihood ratio of 24.3, 24.3 and 12.15, respectively. DISCUSSIONS A wide set of endoscopic markers, including the duodenal bulb, were evaluated in this study. Our results showed that the endoscopy with a careful examination of the duodenum is a sensitive indicator for CD. ABBREVIATIONS CD = celiac disease, GI = gastrointestinal, VA = villous atrophy, NSAID = nonsteroidal anti-inflammatory drug, Sn = sensitivity, Sp = specificity, PPV = positive predictive value, NPV = negative predictive value, AUC = area under the curve, ROC = receiver operating characteristics, WLE = white light endoscopy, NBI = narrow band imaging, tTG = tissue transglutaminase, EMA = anti-endomysial antibodies.
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Affiliation(s)
- D V Balaban
- "Dr. Carol Davila" Central Military University Emergency Hospital, Bucharest, Romania ; "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
| | - A Popp
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania ; "Alfred Rusescu" Institute for Mother and Child Care, Bucharest, Romania ; Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Finland
| | - F Vasilescu
- "Dr. Carol Davila" Central Military University Emergency Hospital, Bucharest, Romania
| | - D Haidautu
- "Alfred Rusescu" Institute for Mother and Child Care, Bucharest, Romania
| | - R M Purcarea
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
| | - M Jinga
- "Dr. Carol Davila" Central Military University Emergency Hospital, Bucharest, Romania ; "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
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Giorgio F, Principi M, Losurdo G, Piscitelli D, Iannone A, Barone M, Amoruso A, Ierardi E, Di Leo A. Seronegative Celiac Disease and Immunoglobulin Deficiency: Where to Look in the Submerged Iceberg? Nutrients 2015; 7:7486-7504. [PMID: 26371035 PMCID: PMC4586545 DOI: 10.3390/nu7095350] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Revised: 08/27/2015] [Accepted: 09/02/2015] [Indexed: 02/06/2023] Open
Abstract
In the present narrative review, we analyzed the relationship between seronegative celiac disease (SNCD) and immunoglobulin deficiencies. For this purpose, we conducted a literature search on the main medical databases. SNCD poses a diagnostic dilemma. Villous blunting, intraepithelial lymphocytes (IELs) count and gluten "challenge" are the most reliable markers. Immunohistochemistry/immunofluorescence tissue transglutaminase (tTG)-targeted mucosal immunoglobulin A (IgA) immune complexes in the intestinal mucosa of SNCD patients may be useful. In our experience, tTG-mRNA was similarly increased in seropositive celiac disease (CD) and suspected SNCD, and strongly correlated with the IELs count. This increase is found even in the IELs' range of 15-25/100 enterocytes, suggesting that there may be a "grey zone" of gluten-related disorders. An immune deregulation (severely lacking B-cell differentiation) underlies the association of SNCD with immunoglobulin deficiencies. Therefore, CD may be linked to autoimmune disorders and immune deficits (common variable immunodeficiency (CVID)/IgA selective deficiency). CVID is a heterogeneous group of antibodies dysfunction, whose association with CD is demonstrated only by the response to a gluten-free diet (GFD). We hypothesized a familial inheritance between CD and CVID. Selective IgA deficiency, commonly associated with CD, accounts for IgA-tTG seronegativity. Selective IgM deficiency (sIgMD) is rare (<300 cases) and associated to CD in 5% of cases. We diagnosed SNCD in a patient affected by sIgMD using the tTG-mRNA assay. One-year GFD induced IgM restoration. This evidence, supporting a link between SNCD and immunoglobulin deficiencies, suggests that we should take a closer look at this association.
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Affiliation(s)
- Floriana Giorgio
- Section of Gastroenterology, University Hospital Policlinico, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
| | - Mariabeatrice Principi
- Section of Gastroenterology, University Hospital Policlinico, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
| | - Giuseppe Losurdo
- Section of Gastroenterology, University Hospital Policlinico, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
| | - Domenico Piscitelli
- Section of Pathology, University Hospital Policlinico, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
| | - Andrea Iannone
- Section of Gastroenterology, University Hospital Policlinico, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
| | - Michele Barone
- Section of Gastroenterology, University Hospital Policlinico, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
| | - Annacinzia Amoruso
- Section of Gastroenterology, University Hospital Policlinico, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
| | - Enzo Ierardi
- Section of Gastroenterology, University Hospital Policlinico, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
| | - Alfredo Di Leo
- Section of Gastroenterology, University Hospital Policlinico, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
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Abstract
BACKGROUND Because of its technical characteristics (i.e. 8-fold magnification, capability to inspect the entire small bowel) and minimal invasiveness, videocapsule endoscopy (VCE) has been proposed as a useful tool for managing patients with celiac disease (CD). KEY MESSAGES Although VCE has been found to be highly sensitive and specific in identifying CD endoscopic markers, it is still inadequate to replace esophagogastroduodenoscopy (EGD) with biopsies in the diagnosis of CD. Nevertheless, it represents a reliable alternative in patients unable or unwilling to undergo EGD. Up to now, available studies have failed to identify any correlation between the length of small bowel involvement and the severity of symptoms. The available evidence on the use of VCE in diagnosing CD in equivocal cases (patients with positive serology and negative or nonspecific histology or those with negative serology and histologically proven villous atrophy) is limited, and its role is still under discussion. In CD patients not improving on gluten-free diet, a complete workup is necessary. In patients with nonresponsive (NRCD) or refractory CD (RCD), VCE has been shown to be able not only to detect significant findings, driving further management, but also to rule out major complications. Nevertheless, in this setting, the inability of VCE to take tissue samples and the risk of capsule retention can represent major limitations. CONCLUSIONS At the present time, for diagnostic purposes, VCE can be proposed only in patients unable or unwilling to undergo EGD, whereas it could be useful in some equivocal cases. Conversely, there is no room for VCE either to estimate the length of the small bowel affected by villous atrophy or to follow up patients improving on gluten-free diet. In patients with NRCD or RCD, VCE can play a role, but it should be combined with other diagnostic techniques.
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Redondo-Cerezo E, Sánchez-Capilla AD, De La Torre-Rubio P, De Teresa J. Wireless capsule endoscopy: perspectives beyond gastrointestinal bleeding. World J Gastroenterol 2014; 20:15664-15673. [PMID: 25400450 PMCID: PMC4229531 DOI: 10.3748/wjg.v20.i42.15664] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2014] [Revised: 04/09/2014] [Accepted: 06/26/2014] [Indexed: 02/06/2023] Open
Abstract
Wireless capsule endoscopy (CE) is a technology developed for the endoscopic exploration of the small bowel. The first capsule model was approved by the Food and Drug Administration in 2001, and its first and essential indication was occult gastrointestinal (GI) bleeding. Over subsequent years, this technology has been refined to provide superior resolution, increased battery life, and capabilities to view different parts of the GI tract. Indeed, cases for which CE proved useful have increased significantly over the last few years, with new indications for the small bowel and technical improvements that have expanded its use to other parts of the GI tract, including the esophagus and colon. The main challenges in the development of CE are new devices with the ability to provide therapy, air inflation for a better vision of the small bowel, biopsy sampling systems attached to the capsule and the possibility to guide and move the capsule with an external motion control. In this article we review the current and new indications of CE, and the evolving technological changes shaping this technology, which has a promising potential in the coming future of gastroenterology.
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Petrarca L, Nenna R, Mastrogiorgio G, Florio M, Brighi M, Pontone S. Dyspepsia and celiac disease: Prevalence, diagnostic tools and therapy. World J Methodol 2014; 4:189-196. [PMID: 25332916 PMCID: PMC4202456 DOI: 10.5662/wjm.v4.i3.189] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2014] [Revised: 06/17/2014] [Accepted: 09/10/2014] [Indexed: 02/06/2023] Open
Abstract
The prevalence of dyspepsia is up to 40% in population-based study. Functional dyspepsia is an exclusion diagnosis and it is classified as a chronic abdominal pain-related functional disorder, characterized by the presence of persistent or recurrent pain or discomfort centered in the upper abdomen, neither relief by defecation, nor association with the onset of a change in stool frequency or form. Celiac disease (CD) is a common autoimmune enteropathy, with a prevalence around 1% in the general population. Its diagnosis includes a serological screening and an upper gastrointestinal endoscopy with multiple biopsies. Gluten-free diet is the only effective treatment. CD diagnosis is often delayed in asymptomatic patients or in individuals with less clinical gastrointestinal symptoms. Several studies performed coeliac disease screening in patients with symptoms suggestive of dyspepsia, showing a biopsy-proved prevalence that ranged from 0.5% to 2%. The typical endoscopic markers of villous atrophy are not sufficiently sensitive, so some endoscopic techniques, such as “water immersion” and confocal endomicroscopy were proposed to improve the diagnostic sensitivity and target biopsies. A recent meta-analysis estimated that the prevalence of CD was higher in patients with dyspepsia, but not in a statistically significant way. However this assumption should be confirmed further larger studies.
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