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Kubas A, Małecka-Wojciesko E. Malignancies in Celiac Disease-A Hidden Threat with Diagnostic Pitfalls. Biomedicines 2025; 13:1507. [PMID: 40564226 DOI: 10.3390/biomedicines13061507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2025] [Revised: 06/10/2025] [Accepted: 06/16/2025] [Indexed: 06/28/2025] Open
Abstract
Celiac disease (CeD) is an autoimmune disorder that is triggered by gluten ingestion in genetically predisposed individuals. Untreated or poorly controlled CeD leads to various disease complications, such as malnutrition, osteoporosis, autoimmune diseases, or refractory celiac disease (RCD). Accumulating recent research has highlighted the association between CeD and the development of malignancies, particularly enteropathy-associated T-cell lymphoma (EATL) and small bowel carcinoma (SBC), which are neoplasms with extremely poor prognoses. Genetic alterations in the JAK1-STAT3 pathway and the high prevalence of microsatellite instability may be the main drivers of CeD-associated lymphomagenesis and small bowel oncogenesis and therefore could be an attractive therapeutic target to block cancer transformation. However, to date, the risk factors and exact mechanisms underlying malignancy development in patients with CeD remain unclear, and prospective cohort studies that include molecular profiling are needed. Moreover, current guidelines on the management of CeD do not provide standardized protocols for cancer surveillance-particularly regarding screening intervals, risk stratification, and monitoring strategies for high-risk patients such as those with RCD. This paper reviews the existing knowledge on malignancies in CeD, highlights diagnostic challenges, and discusses future perspectives on the early detection, monitoring, and treatment of CeD-associated neoplasms.
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Affiliation(s)
- Aleksandra Kubas
- Department of Digestive Tract Diseases, Medical University of Lodz, Kopcinskiego 22, 90-153 Lodz, Poland
| | - Ewa Małecka-Wojciesko
- Department of Digestive Tract Diseases, Medical University of Lodz, Kopcinskiego 22, 90-153 Lodz, Poland
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Haider MB, Al Sbihi A, Reddy SN, Green P. Prevalence of malignant neoplasms in celiac disease patients - a nationwide United States population-based study. World J Clin Oncol 2024; 15:1048-1060. [PMID: 39193153 PMCID: PMC11346075 DOI: 10.5306/wjco.v15.i8.1048] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 06/10/2024] [Accepted: 06/27/2024] [Indexed: 08/16/2024] Open
Abstract
BACKGROUND Celiac disease (CeD) is an autoimmune disorder triggered by the immune response to gluten in genetically predisposed individuals. Recent research has unveiled a heightened risk of developing specific malignant neoplasms (MN) and various malignancies, including gastrointestinal, lymphomas, skin, and others, in individuals with CeD. AIM To investigate the prevalence of MN in hospitalized CeD patients in the United States. METHODS Using data from the National Inpatient Sample spanning two decades, from January 2000 to December 2019, we identified 529842 CeD patients, of which 78128 (14.75%) had MN. Propensity score matching, based on age, sex, race, and calendar year, was employed to compare CeD patients with the general non-CeD population at a 1:1 ratio. RESULTS Positive associations were observed for several malignancies, including small intestine, lymphoma, nonmelanoma skin, liver, melanoma skin, pancreas myelodysplastic syndrome, biliary, stomach, and other neuroendocrine tumors (excluding small and large intestine malignant carcinoid), leukemia, uterus, and testis. Conversely, CeD patients exhibited a reduced risk of respiratory and secondary malignancies. Moreover, certain malignancies showed null associations with CeD, including head and neck, nervous system, esophagus, colorectal, anus, breast, malignant carcinoids, bone and connective tissues, myeloma, cervix, and ovary cancers. CONCLUSION Our study is unique in highlighting the detailed results of positive, negative, or null associations between different hematologic and solid malignancies and CeD. Furthermore, it offers insights into evolving trends in CeD hospital outcomes, shedding light on advancements in its management over the past two decades. These findings contribute valuable information to the understanding of CeD's impact on health and healthcare utilization.
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Affiliation(s)
- Maryam Bilal Haider
- Department of Gastroenterology, Northshore University Health System, Evanston, IL 60201, United States
| | - Ali Al Sbihi
- Department of Hematology/Oncology, University of Miami Miller School of Medicine, Miami, FL 33101, United States
| | - Sushmitha Nanja Reddy
- Department of Hematology/Oncology, Karmanos Cancer Institute/Wayne State University, Detroit, MI 48235, United States
| | - Peter Green
- Celiac Disease Center, Columbia University, New York, NY 10032, United States
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Increased Risk of Colorectal Cancer in Patients With Celiac Disease: A Population-Based Study. Cureus 2023; 15:e36964. [PMID: 37009368 PMCID: PMC10065125 DOI: 10.7759/cureus.36964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/31/2023] [Indexed: 04/03/2023] Open
Abstract
Background and aim: The association between celiac disease (CD) and the development of small bowel lymphoproliferative disorders and esophageal adenocarcinoma has been established in the literature. However, there is only a little evidence demonstrating an increased risk of colorectal cancer (CRC) in patients with CD. Hence, we conducted a cross-sectional population-based study to evaluate the risk of developing CRC in patients who have had a diagnosis of CD. Methodology: We used a commercial database (Explorys Inc, Cleveland, OH), which includes electronic health records from 26 major integrated US healthcare systems. Patients aged 18-65 years were included. Patients with inflammatory bowel disease (IBD) were excluded. Multivariate analysis using backward stepwise logistic regression was performed to calculate the risk of developing CRC in potential confounders. A two-sided P-value <0.05 was considered statistically significant. Results: 79,843,332 individuals were screened in the database and 47,400,960 were selected in the final analysis after accounting for inclusion and exclusion criteria. Using a stepwise multivariate regression analysis, the odds of having CRC among patients with CD was 10.18 (95% CI 9.72-10.65) (P-value <0.001). The odds also remained high among males 1.49 (95% CI 1.36-1.63), African Americans 1.51 (95% CI 1.35-1.68), patients who have type 2 diabetes mellitus (T2DM) 2.71 (95% CI 2.66-2.76), are smokers 2.49 (95% CI 2.44-2.54), are obese 2.21 (95% CI 2.17-2.25), and are alcoholic 1.72 (95% CI 1.66-1.78). Conclusion: Our study demonstrates that patients with CD are frequently found to have CRC even when adjusting for common risk factors. This adds to the literature and helps spread awareness to clinicians that the effects of CD are not only limited to the small bowel as the disease tends to involve other parts of the gastrointestinal tract also, especially the colon. The threshold to screen patients with CD should be considered to be lowered.
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Packova B, Kohout P, Dastych M, Prokesova J, Grolich T, Kroupa R. Malignant complications of celiac disease: a case series and review of the literature. J Med Case Rep 2022; 16:460. [PMID: 36503568 PMCID: PMC9743581 DOI: 10.1186/s13256-022-03682-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 11/18/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Celiac disease is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. Diagnosis is based on evaluating specific autoantibodies and histopathologic findings of duodenal biopsy specimens. The only therapy for celiac disease is a gluten-free diet. Celiac disease can be complicated by malnutrition, other autoimmune diseases, refractoriness to treatment, and gastrointestinal tumors. This article presents seven cases of malignancies in patients with celiac disease. Its objective is to raise awareness of the malignant complications of celiac disease, leading to earlier diagnosis and improved outcomes. CASE PRESENTATION Seven cases of malignant complications of celiac disease occurred among 190 patients followed at the Department of Internal Medicine and Gastroenterology, University Hospital Brno from 2014 to 2021. We describe these cases and the presentation, diagnostic process, course, management, and outcomes for each, along with proposed potential risk factors of malignant complications. There was one Caucasian man who was 70 years old and six Caucasian women who were 36, 46, 48, 55, 73, and 82 years old in our cohort. Of the seven cases of malignancies in our cohort, four patients were diagnosed with small bowel adenocarcinoma, one with diffuse large B-cell lymphoma, one with carcinoma of the tongue, and one with colorectal carcinoma. CONCLUSIONS Malignancies occurred in 3.7% of patients followed up for celiac disease. Awareness of the malignant complications of celiac disease, risk factors, presentation, and disease course could lead to earlier diagnosis and improved outcomes.
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Affiliation(s)
- Barbora Packova
- Department of Internal Medicine and Gastroenterology, University Hospital Brno, Faculty of Medicine, Masaryk University, Jihlavska 20, 62500 Brno, Czech Republic
| | - Pavel Kohout
- grid.4491.80000 0004 1937 116XDepartment of Internal Medicine, Third Faculty of Medicine, Charles University Prague and Teaching Thomayer Hospital, 14059 Prague, Czech Republic
| | - Milan Dastych
- Department of Internal Medicine and Gastroenterology, University Hospital Brno, Faculty of Medicine, Masaryk University, Jihlavska 20, 62500 Brno, Czech Republic
| | - Jitka Prokesova
- Department of Internal Medicine and Gastroenterology, University Hospital Brno, Faculty of Medicine, Masaryk University, Jihlavska 20, 62500 Brno, Czech Republic
| | - Tomas Grolich
- Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic
| | - Radek Kroupa
- Department of Internal Medicine and Gastroenterology, University Hospital Brno, Faculty of Medicine, Masaryk University, Jihlavska 20, 62500 Brno, Czech Republic
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Thompson JS, Mannon P. Celiac disease and the surgeon. Am J Surg 2022; 224:332-338. [PMID: 35221098 DOI: 10.1016/j.amjsurg.2022.02.048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 02/14/2022] [Accepted: 02/16/2022] [Indexed: 11/16/2022]
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Pelizzaro F, Marsilio I, Fassan M, Piazza F, Barberio B, D’Odorico A, Savarino EV, Farinati F, Zingone F. The Risk of Malignancies in Celiac Disease-A Literature Review. Cancers (Basel) 2021; 13:5288. [PMID: 34771450 PMCID: PMC8582432 DOI: 10.3390/cancers13215288] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 10/15/2021] [Accepted: 10/19/2021] [Indexed: 12/14/2022] Open
Abstract
Celiac disease (CeD) is an immune-mediated enteropathy precipitated by ingestion of gluten in genetically predisposed individuals. Considering that CeD affects approximately 1% of the Western population, it may be considered a global health problem. In the large majority of cases, CeD has a benign course, characterized by the complete resolution of symptoms and a normal life expectancy after the beginning of a gluten-free-diet (GFD); however, an increased risk of developing malignancies, such as lymphomas and small bowel carcinoma (SBC), has been reported. In particular, enteropathy-associated T-cell lymphoma (EATL), a peculiar type of T-cell lymphoma, is characteristically associated with CeD. Moreover, the possible association between CeD and several other malignancies has been also investigated in a considerable number of studies. In this paper, we aim to provide a comprehensive review of the current knowledge about the associations between CeD and cancer, focusing in particular on EATL and SBC, two rare but aggressive malignancies.
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Affiliation(s)
- Filippo Pelizzaro
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Ilaria Marsilio
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Matteo Fassan
- Surgical Pathology and Cytopathology Unit, Department of Medicine (DIMED), University Hospital of Padova, 35128 Padova, Italy;
- Veneto Oncology Institute, IOV-IRCCS, 35128 Padova, Italy
| | - Francesco Piazza
- Department of Medicine, Hematology, University Hospital of Padova, 35128 Padova, Italy;
| | - Brigida Barberio
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Anna D’Odorico
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Edoardo V. Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Fabio Farinati
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Fabiana Zingone
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
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Wang M, Yu M, Kong WJ, Cui M, Gao F. Association between intestinal neoplasms and celiac disease: A review. World J Gastrointest Oncol 2021; 13:1017-1028. [PMID: 34616509 PMCID: PMC8465454 DOI: 10.4251/wjgo.v13.i9.1017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 06/02/2021] [Accepted: 07/30/2021] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is a chronic immune-mediated intestinal disease with genetic susceptibility. It is characterized by inflammatory damage to the small intestine after ingestion of cereals and products containing gluten protein. In recent years, the global prevalence rate of CD has been approximately 1%, and is gradually increasing. CD patients adhere to a gluten-free diet (GFD) throughout their entire life. However, it is difficult to adhere strictly to a GFD. Untreated CD may be accompanied by gastrointestinal symptoms, such as diarrhea, abdominal pain, and extraintestinal symptoms caused by secondary malnutrition. Many studies have suggested that CD is associated with intestinal tumors such as enteropathy-associated T-cell lymphoma (EATL), small bowel cancer (SBC), and colorectal cancer. In this study, we reviewed related studies published in the literature to provide a reference for the prevention and treatment of intestinal tumors in patients with CD. Compared with the general population, CD patients had a high total risk of SBC and EATL, but not colorectal cancer. The protective effect of GFD on CD-related malignancies is controversial. Further studies are needed to confirm whether GFD treatment can reduce the risk of intestinal neoplasms in CD.
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Affiliation(s)
- Man Wang
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Ming Yu
- Department of General Practice, Xiangyang Central Hospital, The Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021 Hubei Province, China
| | - Wen-Jie Kong
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Mei Cui
- Department of Pathology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Feng Gao
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
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Marafini I, Monteleone G, Stolfi C. Association Between Celiac Disease and Cancer. Int J Mol Sci 2020; 21:ijms21114155. [PMID: 32532079 PMCID: PMC7312081 DOI: 10.3390/ijms21114155] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 06/08/2020] [Accepted: 06/09/2020] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is a chronic enteropathy that develops in genetically susceptible individuals after the ingestion of gluten. There has been a substantial increase in CD prevalence in the last 50 years, and it is now estimated that this disease affects approximately 1% of the population in the Western world. In the large majority of cases, CD is a benign disease, characterized by the complete resolution of symptoms and a normal life expectancy after the onset of a gluten-free diet (GFD). However, failure to adhere to a strict GFD bears the risk of adverse events and increases mortality. A considerable number of studies have considered the possible association between CD and neoplasms. In particular, an increased risk of malignancies, such as cancers of the gastrointestinal tract and intestinal lymphomas, has been reported. In this review, we summarize and discuss the current evidence on the possible association between CD and cancer.
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Affiliation(s)
- Irene Marafini
- Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (I.M.); (G.M.)
- Gastroenterology Unit, Policlinico Tor Vergata, 00133 Rome, Italy
| | - Giovanni Monteleone
- Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (I.M.); (G.M.)
- Gastroenterology Unit, Policlinico Tor Vergata, 00133 Rome, Italy
| | - Carmine Stolfi
- Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (I.M.); (G.M.)
- Division of Clinical Biochemistry and Clinical Molecular Biology, University of Rome “Tor Vergata”, 00133 Rome, Italy
- Correspondence: ; Tel.: +39-06-72596163
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Colorectal Adenoma Risk Is Increased among Recently Diagnosed Adult Celiac Disease Patients. Gastroenterol Res Pract 2018; 2018:6150145. [PMID: 29849594 PMCID: PMC5937376 DOI: 10.1155/2018/6150145] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2017] [Accepted: 03/18/2018] [Indexed: 12/19/2022] Open
Abstract
Background The association between celiac disease and colorectal neoplasia has been previously studied, but the question whether recently diagnosed celiac patients show an increased colorectal adenoma prevalence remains unanswered. Aims To compare the prevalence of colorectal adenomas between adult patients with a recent diagnosis of celiac disease versus healthy controls. Materials and Methods A retrospective case-control study was undertaken. Patients with a diagnosis of celiac disease at an age of 45 years or more who undertook colonoscopy six months before or six months after the initiation of a gluten-free diet were enrolled as cases. Asymptomatic subjects undertaking screening colonoscopy were recruited as controls in a 2 : 1 fashion. The prevalence of colorectal adenomas and the prevalence of advanced adenomas were compared between groups. Results 57 celiac disease patients and 118 controls were enrolled. There was a greater prevalence of female patients among the celiac group, with no significant differences in terms of age. There were more obese patients among controls and a higher proportion of tabaquism among celiac patients. Adenoma prevalence was significantly higher among celiac patients (47.37% versus 27.97%, p = 0.01). Advanced adenoma detection was not different between groups. Conclusion Adult patients with a recent diagnosis of celiac disease have an increased prevalence of colorectal adenomas.
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Lasa J, Rausch A, Zubiaurre I. Risk of colorectal adenomas in patients with celiac disease: a systematic review and meta-analysis. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2018. [DOI: 10.1016/j.rgmxen.2018.03.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
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Lasa J, Rausch A, Zubiaurre I. Risk of colorectal adenomas in patients with celiac disease: a systematic review and meta-analysis. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2018; 83:91-97. [PMID: 29422261 DOI: 10.1016/j.rgmx.2017.05.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Accepted: 05/31/2017] [Indexed: 02/09/2023]
Abstract
INTRODUCTION AND AIMS Whether celiac disease increases the risk of presenting with colorectal adenoma or not, has not been extensively evaluated. This question becomes relevant when considering early screening methods in patients with the disease. The aim of our article was to determine the risk of colorectal adenomas in celiac disease patients. MATERIALS AND METHODS A computer-assisted search of the MEDLINE-Pubmed, EMBASE, LILACS, Cochrane Library, and Google Scholar databases was carried out, encompassing the time frame of 1966 to December 2016. The search strategy consisted of the following MESH terms: 'celiac disease' OR 'celiac sprue' AND 'colorectal' OR 'colorectal neoplasia' OR 'colorectal adenoma'. A fixed-effect model was used for the analyses. The first analysis dealt with the prevalence of all presentations of colorectal adenoma in patients with celiac disease and the second was on the prevalence of advanced adenomas. The outcomes were described as odds ratios (OR) with their 95% confidence intervals. RESULTS The search identified 480 bibliographic citations, 17 of which were chosen for evaluation. Fourteen of those studies were rejected, leaving a final total of three for the analysis. Those studies included 367 cases of celiac disease and 682 controls. No significant heterogeneity was observed (I2=26%). There was no increased prevalence of colorectal adenomas in the celiac disease patients, when compared with the controls (OR: 0.94 [0.65-1.38]), and no significant difference was observed when assessing the prevalence of advanced adenomas (OR: 0.97 [0.48-1.97]). CONCLUSION Celiac disease was not associated with an increased risk of colorectal adenomas. However, due to the limited evidence available, more studies are necessary to determine whether there is an actual association.
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Affiliation(s)
- J Lasa
- Departamento de Gastroenterología, Hospital Británico, Buenos Aires, Argentina.
| | - A Rausch
- Departamento de Gastroenterología, Hospital Británico, Buenos Aires, Argentina
| | - I Zubiaurre
- Departamento de Gastroenterología, Hospital Británico, Buenos Aires, Argentina
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Abstract
Coeliac disease occurs in about 1% of people in most populations. Diagnosis rates are increasing, and this seems to be due to a true rise in incidence rather than increased awareness and detection. Coeliac disease develops in genetically susceptible individuals who, in response to unknown environmental factors, develop an immune response that is subsequently triggered by the ingestion of gluten. The disease has many clinical manifestations, ranging from severe malabsorption to minimally symptomatic or non-symptomatic presentations. Diagnosis requires the presence of duodenal villous atrophy, and most patients have circulating antibodies against tissue transglutaminase; in children, European guidelines allow a diagnosis without a duodenal biopsy provided that strict symptomatic and serological criteria are met. Although a gluten-free diet is an effective treatment in most individuals, a substantial minority develop persistent or recurrent symptoms. Difficulties adhering to a gluten-free diet have led to the development of non-dietary therapies, several of which are undergoing trials in human beings.
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Affiliation(s)
- Benjamin Lebwohl
- Celiac Disease Center, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University Medical Center, New York, NY, USA
| | - David S Sanders
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital & University of Sheffield, UK
| | - Peter H R Green
- Celiac Disease Center, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA.
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Incidence of malignancies in diagnosed celiac patients: a population-based estimate. Am J Gastroenterol 2014; 109:1471-7. [PMID: 25047399 DOI: 10.1038/ajg.2014.194] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2013] [Accepted: 05/31/2014] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The association between celiac disease and malignancies is well recognized. In Finland, the prevalence of clinically diagnosed adult celiac disease is 0.6%. In this large, population-based cohort, we aimed at a realistic projection of the cancer risk. METHODS In the period 2002-2011, the register comprised 32,439 adult celiac patients. This was linked with the Finnish Cancer Registry, which covers over 98% of diagnosed malignancies. The standardized incidence ratio (SIR) was calculated for the malignancies, on the basis of incidence figures for the whole population. A time-stratified analysis was made in celiac patients diagnosed after 2004 (n=11,991). Lifestyle factors, including smoking habits and obesity, were not obtainable. RESULTS The overall incidence ratio of malignant diseases was not increased (SIR 0.94; 95% confidence intervals 0.89-0.98), but it was ≥5 years from the diagnosis of celiac disease (1.31, 1.04-1.63). The SIRs for non-Hodgkin lymphoma (NHL; 1.94; 1.62-2.29), small-intestinal cancer (4.29; 2.83-6.24), colon cancer (1.35; 1.13-1.58), and basal cell carcinoma of the skin (1.13; 1.03-1.22) were increased, whereas those for lung cancer (0.60; 0.48-0.74), pancreatic cancer (0.73; 0.53-0.97), bladder cancer (0.53; 0.35-0.77), renal cancer (0.72; 0.51-0.99), and breast cancer (0.70; 0.62-0.79) were decreased. SIR for NHL immediately after the diagnosis of celiac disease was 2.56 (1.37-4.38). CONCLUSIONS There was no increased SIR of cancer in the whole series, but SIR was increased after 5 years from the diagnosis of celiac disease. The risk of breast and lung cancers was decreased. The risk of small-intestinal cancer and NHL was increased, but to a lesser extent than previously described.
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Volta U, Vincentini O, Quintarelli F, Felli C, Silano M. Low risk of colon cancer in patients with celiac disease. Scand J Gastroenterol 2014; 49:564-8. [PMID: 24621303 DOI: 10.3109/00365521.2014.893012] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Celiac disease (CD) has strongly been established as associated with some site-specific gastrointestinal malignancies. On the contrary, according to the few reports available, the risk of colon carcinoma in CD patients has been described similar to that of general population. In this cohort study, we describe the risk of colon carcinoma in a group of Italian celiac patients. MATERIALS AND METHODS The study population included all CD patients diagnosed at the Collaborating Centers of the Italian Registry of CD between 1st January 1982 and 31st December 2006. Upon diagnosis of CD and upon at every subsequent clinical control, the Collaborating Centers filled in a validated form for each CD patient reporting information about demographic data, possible occurrence of a neoplasm and adherence to a gluten-free diet. RESULTS Out of 1757 celiac patients enrolled, 6 developed a colon carcinoma during the follow-up period (mean: 18.1 years). The standardized incidence ratio (SIR) resulted 0.29 (95% CI=0.07-0.45). Stratifying the risk for the dietary gluten intake, the SIR dropped to 0.07 (95% CI=0.009-0.27) for CD patients with a strict adherence to a gluten-free diet. CONCLUSION We confirm the previous finding that there is low risk to develop a colon cancer in celiac patients.
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Affiliation(s)
- Umberto Volta
- Department of Medical and Surgical Sciences/Digestive Diseases and Internal Medicine, St. Orsola-Malpighi Hospital , Bologna , Italy
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Risk of colorectal neoplasia in patients with celiac disease: a multicenter study. J Crohns Colitis 2013; 7:e672-7. [PMID: 23845233 DOI: 10.1016/j.crohns.2013.06.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2013] [Revised: 06/11/2013] [Accepted: 06/11/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS The association of celiac disease with colorectal neoplasia is controversial. The aim of this study was to determine the risk of colorectal neoplasia among patients with celiac disease. METHODS We carried out a multicenter, retrospective case-control study, within four community hospitals. Celiac disease patients with a complete colonoscopy were regarded as cases and those without celiac disease as controls. For each case, two controls matched for age, sex, indication for colonoscopy and colorectal cancer family history, were randomly selected. The main outcome evaluated was risk of colorectal polyps, adenomas, advanced neoplastic lesions and cancer. RESULTS We identified 118 patients with celiac disease and 236 controls. The risk of polyps, adenomas and advanced neoplastic lesions was similar in both groups (OR 1.25, CI 0.71-2.18, p=0.40; OR 1.39, CI 0.73-2.63, p=0.31; and OR 1.00, CI 0.26-3.72, p=1.00, respectively). On multivariate analysis, age >75 years old, and first-grade CRC family history were associated with adenomas (OR 2.68 CI 1.03-6.98, OR 6.68 CI 1.03-47.98 respectively) and advanced neoplastic lesions (OR 15.03, CI 2.88-78.3; OR 6.46 CI 1.23-33.79, respectively). With respect to celiac disease characteristic, a low adherence to a gluten free diet was independently associated with the presence of adenomas (OR 6.78 CI 1.39-33.20 p=0.01). CONCLUSIONS Celiac disease was not associated with an increased risk of colorectal neoplasia. Nonadherence to a strict gluten free diet was associated with the presence of adenomas. Further studies addressing celiac disease characteristics are needed to confirm this observation.
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Rostami Nejad M, Aldulaimi D, Ishaq S, Ehsani-Ardakani MJ, Zali MR, Malekzadeh R, Rostami K. Geographic trends and risk of gastrointestinal cancer among patients with celiac disease in Europe and Asian-Pacific region. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2013; 6:170-7. [PMID: 24834268 PMCID: PMC4017519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/26/2013] [Accepted: 08/10/2013] [Indexed: 11/27/2022]
Abstract
Celiac disease is an autoimmune disorder that affects genetically predisposed individuals upon the ingestion of gluten. It is now considered one of the most common genetic disorders in Europe and Asian Pacific region with a prevalence of up to 2.67% of the population. The true prevalence of celiac disease may still be underestimated. Studies remain limited by sample size and selection bias. Celiac disease predisposes to the development of gastrointestinal malignancies, especially lymphomas and small bowel adenocarcinoma. The risk of developing a celiac disease associated malignancies remains uncertain, despite numerous studies. In Middle Eastern countries, the literature regarding celiac disease has expanded significantly in recent years. These studies reported have largely concentrated on the epidemiology of Celiac disease and there is an absolute and relative paucity of published research regarding celiac disease associated malignancy. The aim of this article is to review the current literature and evaluate the risk of gastrointestinal malignancies among patients with celiac disease and then review studies from the Asian Pacific region of the world.
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Affiliation(s)
- Mohammad Rostami Nejad
- Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - David Aldulaimi
- Department of Gastroenterology, Alexandra Hospital, Worcestershire, United Kingdom
| | - Sauid Ishaq
- Gastroenterology Department, Dudley Group of Hospital, Dudley, United Kingdom
| | | | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Reza Malekzadeh
- Digestive Disease Research Institute, Tehran University of Medical Science, Tehran, Iran
| | - Kamran Rostami
- Department of Gastroenterology, Luton & Dunstable Hospital NHS Foundation Trust, Luton, United Kingdom
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Lebwohl B, Tennyson CA, Holub JL, Lieberman DA, Neugut AI, Green PH. Sex and racial disparities in duodenal biopsy to evaluate for celiac disease. Gastrointest Endosc 2012; 76:779-85. [PMID: 22732871 PMCID: PMC3445758 DOI: 10.1016/j.gie.2012.05.011] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2012] [Accepted: 05/09/2012] [Indexed: 12/13/2022]
Abstract
BACKGROUND Celiac disease (CD) is common but underdiagnosed in the United States. Serological screening studies indicate that, although CD occurs at the same frequency in both sexes, women are diagnosed more frequently than men (2:1). CD is less frequently diagnosed among black patients, though the seroprevalence in this group is not known. OBJECTIVE To measure the rates of duodenal biopsy during EGD for symptoms consistent with CD. DESIGN Retrospective cohort study. SETTING Clinical Outcomes Research Initiative National Endoscopy Database, spanning the years 2004 through 2009. PATIENTS Adults undergoing EGD for the indication of diarrhea, anemia, iron deficiency, or weight loss, in which the endoscopic appearance of the upper GI tract was normal. MAIN OUTCOME MEASUREMENT Performance of duodenal biopsy. RESULTS Of 13,091 individuals (58% female patients, 9% black patients) who met the inclusion criteria, duodenal biopsy was performed in 43%, 45% of female patients and 39% of male patients (P < .0001). Black patients underwent duodenal biopsy in 28% of EGDs performed compared with 44% for white patients (P < .0001). On multivariate analysis, male sex (odds ratio [OR] 0.81; 95% CI, 0.75-0.88), older age (OR for 70 years and older compared with 20-49 years, 0.51; 95% CI, 0.46-0.57), and black patients (OR 0.55; 95% CI, 0.48-0.64) were associated with decreased odds of duodenal biopsy. LIMITATIONS Lack of histopathologic correlation with CD prevalence. CONCLUSIONS In this multiregional endoscopy database spanning the period from 2004 through 2009, rates of duodenal biopsy increased modestly over time, but overall remained low in patients with possible clinical indications for biopsy. Nonperformance of duodenal biopsy during endoscopy may be contributing to the underdiagnosis of CD in the United States.
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Affiliation(s)
- Benjamin Lebwohl
- Celiac Disease Center, Department of Medicine, Columbia University Medical Center
- Department of Epidemiology, Mailman School of Public Health, Columbia University
| | | | - Jennifer L. Holub
- Department of Gastroenterology, Oregon Health & Science University, Portland, OR
| | - David A. Lieberman
- Department of Gastroenterology, Oregon Health & Science University, Portland, OR
| | - Alfred I. Neugut
- Celiac Disease Center, Department of Medicine, Columbia University Medical Center
- Department of Epidemiology, Mailman School of Public Health, Columbia University
| | - Peter H.R. Green
- Celiac Disease Center, Department of Medicine, Columbia University Medical Center
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Abstract
This article reviews the risk of mortality and malignancy in celiac disease (CD) and examines the evidence of the protective effect of a gluten-free diet (GFD) on mortality and malignancy. Population-based studies have confirmed that patients with diagnosed CD are at increased risk of mortality. However, patients with CD do not seem to be at an increased risk of malignancy, except for an increased risk of lymphoproliferative malignancy and gastrointestinal cancer. The evidence that a GFD reduces the risk of mortality is weak, but there is some evidence suggesting that a GFD may reduce the risk of lymphoproliferative malignancy.
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Jones J. Wheat Belly—An Analysis of Selected Statements and Basic Theses from the Book. CEREAL FOOD WORLD 2012. [DOI: 10.1094/cfw-57-4-0177] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Affiliation(s)
- J. Jones
- St. Catherine University, St. Paul, MN, U.S.A
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Increased sedation requirements during endoscopy in patients with celiac disease. Dig Dis Sci 2012; 57:994-9. [PMID: 22052448 DOI: 10.1007/s10620-011-1959-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2011] [Accepted: 10/20/2011] [Indexed: 12/13/2022]
Abstract
BACKGROUND Celiac disease (CD) is associated with increased rates of neuropsychiatric disease and irritable bowel syndrome, and patients may exhibit visceral hypersensitivity. AIM The purpose of this study was to determine whether patients with CD have increased sedation requirements during endoscopic procedures. METHODS In this retrospective cohort study, we identified CD patients undergoing either a colonoscopy or esophagogastroduodenoscopy (EGD), but not a dual procedure. CD patients were matched with control patients according to age, gender and endoscopist. For sedation requirements we defined "high" as falling outside of the 75th percentile of the entire cohort. RESULTS In the colonoscopy analysis we identified 113 CD patients and 278 controls. In the CD group, 29 individuals (26%) required high amounts of both opioids and midazolam, as compared to 46 (17%) controls (P = 0.05). Differences were similar when considering only opioids (P = 0.06) and midazolam (P = 0.06). In the EGD analysis we identified 314 CD patients and 314 controls who met the inclusion criteria. Among the CD patients, 70 (22%) required high amounts of both opioids and midazolam compared to 51 (16%) controls (P = 0.05). Differences were similar when considering only opioids (P = 0.06) and midazolam (P = 0.04). CONCLUSIONS Patients with CD require higher doses of sedation during upper and lower endoscopy compared to age and gender-matched controls. Putative explanations, such as visceral hypersensitivity, chronic opioid/anxiolytic use, or underlying neuropsychiatric illness, should be evaluated prospectively.
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Abstract
PURPOSE OF REVIEW This article critically summarizes the recent scientific and clinical advances in coeliac disease. RECENT FINDINGS Epidemiological studies have shown that coeliac disease is as common in parts of Asia, Africa and Eastern Europe as in the western world. Genome-wide association studies continue to identify genetic susceptibilities that are both unique to coeliac disease and overlap with other autoimmune diseases. Human leukocyte antigen genotyping offers additional sensitivity in detecting coeliac disease in individuals who have self-prescribed gluten-free diets (GFD) or have atypical presentations. Immunological advances have highlighted the potential proinflammatory pitfalls of vitamin A supplementation in active coeliac disease and have enabled identification of oat and barley subsets that may be safely incorporated into coeliac diets. Large population-based studies have expanded our knowledge of the long-term risks of coeliac disease, in addition to excluding infertility as a cause for concern once a GFD has been established. SUMMARY The long-term implications of active coeliac disease emphasize the need for early detection and strict adherence to GFD, which remains the cornerstone of management. Technological advances in food modulation and immuno-therapies offer promise, but remain in the translational phases of clinical trials at present.
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Elfström P, Granath F, Ye W, Ludvigsson JF. Low risk of gastrointestinal cancer among patients with celiac disease, inflammation, or latent celiac disease. Clin Gastroenterol Hepatol 2012; 10:30-36. [PMID: 21723236 DOI: 10.1016/j.cgh.2011.06.029] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2011] [Accepted: 06/09/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Celiac disease has been associated with gastrointestinal (GI) cancers in small studies; risks have not been estimated from large populations or based on histopathology analyses. METHODS We examined the risk of GI cancers by using data from cohorts of patients with celiac disease (villous atrophy, Marsh score of 3; n = 28,882) or inflammation (Marsh score of 1-2; n = 12,860); biopsy samples were evaluated at 28 pathology centers. A third cohort included 3705 individuals with latent celiac disease (normal mucosa, but positive serology results). Data were compared with those from an age- and sex-matched population. RESULTS Of patients with celiac disease, 372 developed incident GI cancers; 347 patients with inflammation and 38 with latent celiac disease developed GI cancers. In the first year after diagnosis and initial biopsy, celiac disease was associated with 5.95-fold increase in risk of incident GI cancer (95% confidence interval [CI], 4.64-7.64); the hazard ratio [HR] for inflammation was 9.13 (95% CI, 7.19-11.6) and for latent celiac disease was 8.10 (95% CI, 4.69-14.0). After the first year, patients were at no significant increase in risk for GI cancers; the HR for celiac disease was 1.07 (95% CI, 0.93-1.23), for inflammation it was 1.16 (95% CI, 0.98-1.37), and for latent celiac disease it was 0.96 (95% CI, 0.56-1.66). The absolute risk for any GI cancer in patients with celiac disease was 101/100,000 person-years, with an excess risk of 2/100,000 person-years. CONCLUSIONS Although celiac disease, inflammation, and latent disease all increase risk for GI cancers in the first year after diagnosis, there is no increase in risk thereafter.
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Affiliation(s)
- Peter Elfström
- Department of Neonatology, Astrid Lindgren Children's Hospital-Danderyd, Karolinska University Hospital, Stockholm, Sweden
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