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Cardinaels N, Van Rompaey W, Bos S, Bode H, Tousseyn T, Van Bleyenbergh P. An atypical case of a pulmonary mass in an immunocompromised patient. Acta Clin Belg 2020; 75:370-374. [PMID: 31423951 DOI: 10.1080/17843286.2019.1655232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
OBJECTIVES Pulmonary lymphomatoid granulomatosis (PLG) is a rare angiocentric and angiodestructive EBV-associated lymphoproliferative disorder which almost always affects the lungs. PLG is more commonly diagnosed in patients with immunodeficiency and is associated with Epstein-Barr virus (EBV). 'Drug induced PLG' or 'iatrogenic immunodeficiency-associated lymphoproliferative disorder' is a special form of PLG described in patient with inflammatory bowel diseases treated with Azathioprine. METHODS We report a case of drug-induced PLG in a 68-year-old patient with Crohn's disease presenting with pain at the right hemithorax, fatigue and shortness of breath with a pulmonary mass. RESULTS Although initial diagnostic findings were misleading, an open lung biopsy eventually led to the diagnosis of drug-induced PLG. CONCLUSION The diagnosis of PLG is challenging because the disease is rare and the histological features can be very subtle. Correct diagnosis relies on histopathology and immunohistochemical staining and EBV RNA in situ hybridization with sampling of large and different amounts of pathologic tissue in the hands of expert pathologists. In drug-induced PLG specifically, withdrawal of the immunosuppressive agent can lead to disease regression.
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Affiliation(s)
- Nina Cardinaels
- Department of Pulmonology, University Hospitals Leuven, Leuven, Belgium
| | | | - Saskia Bos
- Department of Pulmonology, University Hospitals Leuven, Leuven, Belgium
| | - Hannelore Bode
- Department of Pulmonology, AZ Delta Roeselare-Menen-Torhout, Belgium
| | - Thomas Tousseyn
- Department of Pathology, University Hospitals Leuven, Leuven, Belgium
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van de Ven SEM, Derikx LAAP, Nagtegaal ID, van Herpen CM, Takes RP, Melchers WJG, Pierik M, van den Heuvel T, Verhoeven RHA, Hoentjen F, Nissen LHC. Laryngeal Carcinoma in Patients With Inflammatory Bowel Disease: Clinical Outcomes and Risk Factors. Inflamm Bowel Dis 2020; 26:1060-1067. [PMID: 31559415 PMCID: PMC7301406 DOI: 10.1093/ibd/izz210] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) patients are at increased risk for developing extra-intestinal malignancies, mainly due to immunosuppressive medication. The risk of developing head and neck cancer in immunosuppressed transplant patients is increased. The relation between IBD patients and laryngeal cancer (LC) remains unclear. We aimed (1) to identify risk factors in IBD patients for LC development and (2) to compare clinical characteristics, outcome, and survival of LC in IBD patients with the general population. METHODS All IBD patients with LC (1993-2011) were retrospectively identified using the Dutch Pathology Database. We performed 2 case-control studies: (1) to identify risk factors, we compared patients with IBD and LC (cases) with the general IBD population; (2) to analyze LC survival, we compared cases with controls from the general LC population. RESULTS We included 55 cases, 1800 IBD controls, and 2018 LC controls. Cases were more frequently male compared with IBD controls (P < 0.001). For ulcerative colitis (UC), cases were older at IBD diagnosis (P < 0.001). Crohn's disease (CD) cases were more frequently tobacco users (P < 0.001) and more often had stricturing (P = 0.006) and penetrating (P = 0.008) disease. We found no survival difference. Immunosuppressive medication had no impact on survival. CONCLUSIONS Male sex was a risk factor for LC in IBD patients. Older age at IBD diagnosis was a risk factor for UC to develop LC. Tobacco use and stricturing and penetrating disease were risk factors for LC development in CD patients. Inflammatory bowel disease was not associated with impaired survival of LC. Immunosuppressive medication had no influence on survival.
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Affiliation(s)
- Steffi E M van de Ven
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Lauranne A A P Derikx
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Iris D Nagtegaal
- Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Carla M van Herpen
- Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - Robert P Takes
- Department of Otolaryngology and Head and Neck Surgery, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Willem J G Melchers
- Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Marieke Pierik
- Department of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Tim van den Heuvel
- Department of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Rob H A Verhoeven
- Department of Research & Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands
| | - Frank Hoentjen
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - L H C Nissen
- Department of Gastroenterology and Hepatology, Jeroen Bosch Hospital, ‘s-Hertogenbosch, the Netherlands,Address correspondence to: Loes H. C. Nissen, PhD, Department of Gastroenterology and Hepatology, Jeroen Bosch Hospital, Henri Dunantstraat 1, Postbox 90153, 5200 ME ‘s-Hertogenbosch, the Netherlands ()
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Bennani A, Kharrasse G, Achraf M, Wafa K, Zahi I, Imane K, Mohamed B. Synchronous colonic adenoma and intestinal marginal zone B-cell lymphoma associated with Crohn's disease: a case report and literature review. BMC Cancer 2019; 19:966. [PMID: 31623635 PMCID: PMC6796348 DOI: 10.1186/s12885-019-6224-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Accepted: 10/09/2019] [Indexed: 12/11/2022] Open
Abstract
Background Lymphoma and dysplasia are rare complications of long-standing Crohn’s disease. We report an exceptional case of a synchronous intestinal marginal zone B-cell lymphoma (MALT lymphoma) and colonic adenoma in a Crohn’s disease patient. Case presentation A 50-year-old male patient presented with right lower quadrant for the last 9 months. He also had associated weight loss and diarrhea alternating with constipation. Ileo-colonoscopy revealed a pseudopolypoid appearance of the colonic and ileal mucosa with many discontinuous ulcerations with a 3 cm sessile polypoid mass at 17 cm from the anal verge. Histological examination of the polypoid lesion revealed an adenoma with high grade dysplasia, while the biopsies of colonic mucosa showed histologic features of Crohn’s disease. Abdominal computed tomography scan (CT scan) and magnetic resonance imaging (MRI) showed circumferential wall thickening of the colon and ileum, enlarged mesenteric lymph nodes and a sessile polypoid mass of the rectosigmoid junction. The patient was scheduled for an ileocoletectomy with resection of the upper rectum and ileorectostomy. The histological examination of the resected segment showed histologic features of Crohn’s disease, a recto-sigmoid polyp with high grade. dysplasia and extensive small lymphocytic infiltrate in both colonic and ileal wall which is strongly stained by CD20 and BCL2. The diagnosis of MALT lymphoma with adenoma on a background of Crohn’s disease was made. The patient successfully completed 8 cycles of Rituximab+ chlorambucil chemotherapy. Nowadays the patient is asymptomatic without evidence of lymphoproliferative recurrence 10 months after surgery. Conclusion We report the first case in the literature of Malt lymphoma with colonic adenoma associated with Crohn’s disease, and discuss his unique macroscopic and histological features in a patient. Without immunosuppressive therapy.
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Affiliation(s)
- Amal Bennani
- Department of pathology, Mohamed I University, 30050, Oujda, Morocco. .,Laboratory of Epidemiology, Clinical Research and Public, Medical School of Oujda, Oujda, Morocco.
| | - Ghizlane Kharrasse
- Department of Gastroenterology, Mohamed I University, 30050, Oujda, Morocco
| | - Miry Achraf
- Department of pathology, Mohamed I University, 30050, Oujda, Morocco
| | - Khanoussi Wafa
- Department of Gastroenterology, Mohamed I University, 30050, Oujda, Morocco
| | - Ismaili Zahi
- Department of Gastroenterology, Mohamed I University, 30050, Oujda, Morocco
| | - Kamaoui Imane
- Department of radiology, Mohamed I University, 30050, Oujda, Morocco
| | - Bouziane Mohamed
- Department of Surgical Oncology, Mohamed I University, 30050, Oujda, Morocco
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Cromer WE, Zawieja DC. Acute exposure to space flight results in evidence of reduced lymph Transport, tissue fluid Shifts, and immune alterations in the rat gastrointestinal system. LIFE SCIENCES IN SPACE RESEARCH 2018; 17:74-82. [PMID: 29753416 DOI: 10.1016/j.lssr.2018.03.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Revised: 03/09/2018] [Accepted: 03/19/2018] [Indexed: 06/08/2023]
Abstract
Space flight causes a number of alterations in physiological systems, changes in the immunological status of subjects, and altered interactions of the host to environmental stimuli. We studied the effect of space flight on the lymphatic system of the gastrointestinal tract which is responsible for lipid transport and immune surveillance which includes the host interaction with the gut microbiome. We found that there were signs of tissue damage present in the space flown animals that was lacking in ground controls (epithelial damage, crypt morphological changes, etc.). Additionally, morphology of the lymphatic vessels in the tissue suggested a collapsed state at time of harvest and there was a profound change in the retention of lipid in the villi of the ileum. Contrary to our assumptions there was a reduction in tissue fluid volume likely associated with other fluid shifts described. The reduction of tissue fluid volume in the colon and ileum is a likely contributing factor to the state of the lymphatic vessels and lipid transport issues observed. There were also associated changes in the number of MHC-II+ immune cells in the colon tissue, which along with reduced lymphatic competence would favor immune dysfunction in the tissue. These findings help expand our understanding of the effects of space flight on various organ systems. It also points out potential issues that have not been closely examined and have to potential for the need of countermeasure development.
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Affiliation(s)
- W E Cromer
- Department of Medical Physiology, Texas A&M University Health Science Center, United States.
| | - D C Zawieja
- Department of Medical Physiology, Texas A&M University Health Science Center, United States
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Cao Y, Ding Z, Han C, Shi H, Cui L, Lin R. Efficacy of Mesenchymal Stromal Cells for Fistula Treatment of Crohn's Disease: A Systematic Review and Meta-Analysis. Dig Dis Sci 2017; 62:851-860. [PMID: 28168575 DOI: 10.1007/s10620-017-4453-x] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Accepted: 01/10/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM The introduction of mesenchymal stromal cells (MSCs) has changed the management of Crohn's fistula, while it remains controversial. The aim of this study was to provide an overview of efficacy and optimum state of MSCs treatment on Crohn's fistula. METHODS Studies reporting MSCs treatment on Crohn's fistula were searched and included. A fixed-effects model was used to assess the efficacy of MSCs, and outcomes of healing and recurrence were used to evaluate the best states of MSCs intervention. RESULTS Fourteen articles were enrolled (n = 477). Pooled analysis showed MSCs had a significant efficacy compared to other treatments [risk difference: 0.21 (0.09, 0.32), P = 0.000]. Notably, after MSCs treatment, the group of Crohn's disease activity index (CDAI) baseline >150 group had a higher healing rate (HR) and a clinical response (a change in CDAI of >50 points) (79.17 ± 8.78 vs. 47.54 ± 15.90, P = 0.011) compared to CDAI baseline of <150. The duration time of CD and fistulas had a negative correlation with HR accompanied by MSC therapy (r = -0.900, -0.925). Then, a moderate dose MSCs (2-4 × 107 cells/ml) had a higher HR (80.07%) and lower recurrence rate (RR 13.98%) compared to other dosages. Moreover, adipose-derived MSCs therapy had an advantage over bone marrow-derived MSCs in terms of low RR (7.4 ± 4.28 vs. 13.39 ± 0.89). CONCLUSIONS The evidence supported the effect of MSCs at a more appropriate time of Crohn's fistula. And CDAI baseline (the points >150) has been a candidate for evaluating effectiveness of MSCs application on Crohn's fistula.
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Affiliation(s)
- Yantian Cao
- Division of Gastroenterology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China
| | - Zhen Ding
- Division of Gastroenterology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China
| | - Chaoqun Han
- Division of Gastroenterology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China
| | - Huiying Shi
- Division of Gastroenterology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China
| | - Lianlian Cui
- Division of Gastroenterology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China
| | - Rong Lin
- Division of Gastroenterology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China.
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Ciccocioppo R, Racca F, Scudeller L, Piralla A, Formagnana P, Pozzi L, Betti E, Vanoli A, Riboni R, Kruzliak P, Baldanti F, Corazza GR. Differential cellular localization of Epstein-Barr virus and human cytomegalovirus in the colonic mucosa of patients with active or quiescent inflammatory bowel disease. Immunol Res 2016; 64:191-203. [PMID: 26659090 DOI: 10.1007/s12026-015-8737-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The role of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in the exacerbation of inflammatory bowel disease (IBD) is still uncertain. We prospectively investigated the presence of EBV and HCMV infection in both epithelial and immune cells of colonic mucosa of IBD patients, both refractory and responders to standard therapies, in comparison with patients suffering from irritable bowel syndrome who were considered as controls, by using quantitative real-time polymerase chain reaction, immunohistochemistry and in situ hybridization, in an attempt to assess viral localization, DNA load, life cycle phase and possible correlation with disease activity indexes. We obtained clear evidence of the presence of high DNA loads of both viruses in either enterocytes or immune cells of refractory IBD patients, whereas we observed low levels in the responder group and an absence of detectable copies in all cell populations of controls. Remarkably, the values of EBV and HCMV DNA in inflamed mucosa were invariably higher than in non-inflamed areas in both IBD groups, and the EBV DNA loads in the cell populations of diseased mucosa of refractory IBD patients positively correlated with the severity of mucosal damage and clinical indexes of activity. Moreover, EBV infection resulted the most prevalent either alone or in combination with HCMV, while immunohistochemistry and in situ hybridization did not allow us to distinguish between the different phases of viral life cycle. Finally, as regards treatment, these novel findings could pave the way for the use of new antiviral molecules in the treatment of this condition.
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Affiliation(s)
- Rachele Ciccocioppo
- Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Piazzale Golgi, 19, 27100, Pavia, Italy.
| | - Francesca Racca
- Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Piazzale Golgi, 19, 27100, Pavia, Italy
| | - Luigia Scudeller
- Biometry and Clinical Epidemiology Unit, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Antonio Piralla
- SS Virologia Molecolare - SC Virologia e Microbiologia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Pietro Formagnana
- Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Piazzale Golgi, 19, 27100, Pavia, Italy
| | - Lodovica Pozzi
- Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Piazzale Golgi, 19, 27100, Pavia, Italy
| | - Elena Betti
- Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Piazzale Golgi, 19, 27100, Pavia, Italy
| | - Alessandro Vanoli
- Department of Human Pathology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Roberta Riboni
- Department of Human Pathology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Peter Kruzliak
- 2nd Department of Internal Medicine, St. Anne's University Hospital and Masaryk University, Pekarska 53, 656 91, Brno, Czech Republic. .,Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odborarov 10, 832 32, Bratislava, Slovak Republic.
| | - Fausto Baldanti
- SS Virologia Molecolare - SC Virologia e Microbiologia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.,Department of Clinical Sciences, Surgery, Diagnostics and Pediatrics, University of Pavia, Pavia, Italy
| | - Gino Roberto Corazza
- Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Piazzale Golgi, 19, 27100, Pavia, Italy
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Giagkou E, Christodoulou DK, Katsanos KH. Mouth cancer in inflammatory bowel diseases. Oral Dis 2016; 22:260-4. [DOI: 10.1111/odi.12420] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Revised: 12/06/2015] [Accepted: 12/07/2015] [Indexed: 12/26/2022]
Affiliation(s)
- E Giagkou
- Division of Gastroenterology; School of Health Sciences; University of Ioannina; Ioannina Greece
| | - DK Christodoulou
- Division of Gastroenterology; School of Health Sciences; University of Ioannina; Ioannina Greece
| | - KH Katsanos
- Division of Gastroenterology; School of Health Sciences; University of Ioannina; Ioannina Greece
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Katsanos KH, Roda G, Brygo A, Delaporte E, Colombel JF. Oral Cancer and Oral Precancerous Lesions in Inflammatory Bowel Diseases: A Systematic Review. J Crohns Colitis 2015; 9:1043-52. [PMID: 26163301 DOI: 10.1093/ecco-jcc/jjv122] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2015] [Accepted: 07/03/2015] [Indexed: 12/29/2022]
Abstract
Oral cancer is historically linked to well-known behavioural risk factors such as tobacco smoking and alcohol consumption. Other risk factors include age over 40, male sex, several dietary factors, nutritional deficiencies, viruses, sexually transmitted infections, human papillomavirus, chronic irritation, and possibly genetic predisposition. Precancerous lesions in the oral cavity include leukoplakia, erythroplakia, and lichen planus. Histology of oral cancer varies widely but the great majority are squamous cell carcinomas.Epidemiological studies and cancer registries have shown a consistently increased risk of oral malignancies in kidney, bone marrow, heart, or liver transplantation, in graft vs host disease, and in patients with HIV infection. Because of the increasing use of immunosuppressive drugs in patients with inflammatory bowel disease, it is useful to more accurately delineate the consequences of chronic immunosuppression to the oral cavity. Oral cancer and precancerous oral lesions in patients with inflammatory bowel disease [IBD] have been scarcely reported and reviews on the topic are lacking.We conducted a literature search using the terms and variants of all cancerous and precancerous oral manifestations of inflammatory bowel diseases. By retrieving the existing literature, it is evident that patients with IBD belong to the high-risk group of developing these lesions, a phenomenon amplified by the increasing HPV prevalence. Education on modifiable risk behaviours in patients with oral cancer is the cornerstone of prevention.Oral screening should be performed for all IBD patients, especially those who are about to start an immunosuppressant or biological drug.
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Affiliation(s)
- Konstantinos H Katsanos
- Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Giulia Roda
- Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Alexandre Brygo
- Department of Stomatology, Centre Hospitalier Régional Universitaire de Lille, Lille, France
| | - Emmanuel Delaporte
- Department of Dermatology, Centre Hospitalier Régional Universitaire de Lille, Lille, France
| | - Jean-Frédéric Colombel
- Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Ciccocioppo R, Gallia A, Sgarella A, Kruzliak P, Gobbi PG, Corazza GR. Long-Term Follow-Up of Crohn Disease Fistulas After Local Injections of Bone Marrow-Derived Mesenchymal Stem Cells. Mayo Clin Proc 2015; 90:747-55. [PMID: 26046409 DOI: 10.1016/j.mayocp.2015.03.023] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2015] [Revised: 03/25/2015] [Accepted: 03/31/2015] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To assess the long-term outcome of patients treated with serial intrafistular injections of autologous bone marrow-derived mesenchymal stem cells (MSCs) for refractory Crohn fistulas in terms of safety and efficacy. PATIENTS AND METHODS Starting from January 10, 2007, through June 30, 2014, clinical evaluation, calculation of the Crohn disease activity index (CDAI), therapeutic management, and documentation of adverse events in 8 of the 10 patients (5 men; median age, 37 years) who had been injected locally with MSCs were prospectively recorded for 72 months. Cumulative probabilities of fistula recurrence and medical or surgical treatment were estimated using a Kaplan-Meier method, whereas differences among the pre- and post-MSC CDAI values were calculated with the Mann-Whitney U test. RESULTS Following disease remission observed after 12 months from MSC treatment (P<.001), the mean CDAI score increased significantly during the subsequent 2 years (P=.007), and was then followed by a gradual decrease, with the patients achieving remission again (P=.02) at the end of the 5-year follow-up. The probability of fistula relapse-free survival was 88% at 1 year, 50% at 2 years, and 37% during the following 4 years, and the cumulative probabilities of surgery- and medical-free survival were 100% and 88% at 1 year, 75% and 25% at 2, 3, and 4 years, and 63% and 25% at 5 and 6 years, respectively. No adverse events were recorded. CONCLUSION Locally injected MSCs constitute a safe therapy that rescues refractory patients and regains responsiveness to drugs previously proved ineffective.
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Affiliation(s)
- Rachele Ciccocioppo
- Centre for the Study and Cure of Inflammatory Bowel Disease, Clinica Medica I, IRCCS San Matteo Hospital Foundation, University of Pavia - Piazzale Golgi, Pavia, Italy.
| | - Alessandra Gallia
- Centre for the Study and Cure of Inflammatory Bowel Disease, Clinica Medica I, IRCCS San Matteo Hospital Foundation, University of Pavia - Piazzale Golgi, Pavia, Italy
| | - Adele Sgarella
- Clinica Chirurgica, IRCCS San Matteo Hospital Foundation, University of Pavia - Piazzale Golgi, Pavia, Italy
| | - Peter Kruzliak
- International Clinical Research Center, St Anne's University Hospital and Masaryk University, Pekarska Brno, Czech Republic
| | - Paolo G Gobbi
- Centre for the Study and Cure of Inflammatory Bowel Disease, Clinica Medica I, IRCCS San Matteo Hospital Foundation, University of Pavia - Piazzale Golgi, Pavia, Italy
| | - Gino Roberto Corazza
- Centre for the Study and Cure of Inflammatory Bowel Disease, Clinica Medica I, IRCCS San Matteo Hospital Foundation, University of Pavia - Piazzale Golgi, Pavia, Italy
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10
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Ciccocioppo R, Racca F, Paolucci S, Campanini G, Pozzi L, Betti E, Riboni R, Vanoli A, Baldanti F, Corazza GR. Human cytomegalovirus and Epstein-Barr virus infection in inflammatory bowel disease: Need for mucosal viral load measurement. World J Gastroenterol 2015; 21:1915-1926. [PMID: 25684960 PMCID: PMC4323471 DOI: 10.3748/wjg.v21.i6.1915] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2014] [Revised: 10/03/2014] [Accepted: 11/19/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the best diagnostic technique and risk factors of the human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infection in inflammatory bowel disease (IBD).
METHODS: A cohort of 40 IBD patients (17 refractory) and 40 controls underwent peripheral blood and endoscopic colonic mucosal sample harvest. Viral infection was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry, and correlations with clinical and endoscopic indexes of activity, and risk factors were investigated.
RESULTS: All refractory patients carried detectable levels of HCMV and/or EBV mucosal load as compared to 13/23 (56.5%) non-refractory and 13/40 (32.5%) controls. The median DNA value was significantly higher in refractory (HCMV 286 and EBV 5.440 copies/105 cells) than in non-refractory (HCMV 0 and EBV 6 copies/105 cells; P < 0.05 and < 0.001) IBD patients and controls (HCMV and EBV 0 copies/105 cells; P < 0.001 for both). Refractory patients showed DNA peak values ≥ 103 copies/105 cells in diseased mucosa in comparison to non-diseased mucosa (P < 0.0121 for HCMV and < 0.0004 for EBV), while non-refractory patients and controls invariably displayed levels below this threshold, thus allowing us to differentiate viral colitis from mucosal infection. Moreover, the mucosal load positively correlated with the values found in the peripheral blood, whilst no correlation with the number of positive cells at immunohistochemistry was found. Steroid use was identified as a significant risk factor for both HCMV (P = 0.018) and EBV (P = 0.002) colitis. Finally, a course of specific antiviral therapy with ganciclovir was successful in all refractory patients with HCMV colitis, whilst refractory patients with EBV colitis did not show any improvement despite steroid tapering and discontinuation of the other medications.
CONCLUSION: Viral colitis appeared to contribute to mucosal lesions in refractory IBD, and its correct diagnosis and management require quantitative real-time polymerase chain reaction assay of mucosal specimens.
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Connors W, Griffiths C, Patel J, Belletrutti PJ. Lymphomatoid granulomatosis associated with azathioprine therapy in Crohn disease. BMC Gastroenterol 2014; 14:127. [PMID: 25022612 PMCID: PMC4105046 DOI: 10.1186/1471-230x-14-127] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2014] [Accepted: 06/26/2014] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Lymphomatoid granulomatosis (LYG) is a rare Epstein-Barr virus-associated lymphoproliferative disorder. It most often occurs in patients with immunodeficiency and the clinical course ranges from indolent behavior to that of an aggressive malignancy. Pulmonary, central nervous system and dermatological manifestations are most common. To our knowledge this is the first reported case of LYG related to azathioprine therapy in Crohn disease. CASE PRESENTATION A twenty-six year old Caucasian woman with colonic Crohn disease on maintenance azathioprine therapy presented with right upper quadrant pain and fever. Diagnostic imaging revealed extensive liver, pulmonary and cerebral lesions. A diagnosis of LYG was made based on the pattern of organ involvement and the immunohistochemical features on liver and lung biopsy. CONCLUSIONS Thiopurine therapy for inflammatory bowel disease is associated with an increased incidence of lymphoproliferative disorders. This report highlights the diagnostic challenges associated with LYG. As long-term thiopurine therapy remains central to the management of inflammatory bowel diseases it is essential that both patients and clinicians are aware of this potential adverse outcome.
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Affiliation(s)
| | | | | | - Paul J Belletrutti
- Division of Gastroenterology and Hepatology, University of Calgary, Foothills Medical Centre, Calgary, Canada.
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Drug therapies and the risk of malignancy in Crohn's disease: results from the TREAT™ Registry. Am J Gastroenterol 2014; 109:212-23. [PMID: 24394749 DOI: 10.1038/ajg.2013.441] [Citation(s) in RCA: 123] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2013] [Accepted: 11/04/2013] [Indexed: 02/07/2023]
Abstract
OBJECTIVES We assessed potential associations between malignancy and antitumor necrosis factor therapy in patients with Crohn's disease (CD), as this relationship is currently poorly defined. METHODS Utilizing data from the Crohn's Therapy, Resource, Evaluation, and Assessment Tool (TREAT™) Registry, a prospective cohort study examining long-term outcomes of CD treatments in community and academic settings, influences of baseline patient/disease characteristics and medications were assessed by survival analysis and multivariate models. Standardized incidence ratios and exact 95 % confidence intervals were determined as the ratio of events observed (TREAT) vs. expected (general population of USA). RESULTS As of 23 February 2010, 6,273 CD patients (infliximab during registry=3,420 (during or within 1 year before registry=3,764); other-treatments-only: 2,509), were enrolled and, on average, had been followed for 5.2/7.6 years, respectively, for all/currently active patients. Crude cancer incidences were similar between infliximab- and other-treatments-only-exposed patients. Multivariate Cox regression analysis demonstrated that baseline age (hazard ratio (HR)=1.59/10 years; P<0.001), disease duration (HR=1.64/10 years; P=0.012), and smoking (HR=1.38; P=0.045) but neither immunosuppressive therapy alone (HR=1.43; P=0.11), infliximab therapy alone (HR=0.59; P=0.16), nor their combination (HR=1.22, P=0.34) were independently associated with the risk of malignancy. When compared with the general population, no significant increase in incidence was observed in any malignancy category. In an exposure-based analysis, use of immunosuppressants alone (odds ratio=4.19) or in combination with infliximab (3.33) seemed to be associated with a numerically, but not significantly, greater risk of malignancy than did treatment with infliximab alone (1.96) relative to treatment with neither. CONCLUSIONS In the TREAT Registry, age, disease duration, and smoking were independently associated with increased risk of malignancy. Although results for immunosuppressant use were equivocal, no significant association between malignancy and infliximab was observed.
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Algaba A, Guerra I, Castaño &A, Poza GDL, Castellano VM, López M, Bermejo F. Risk of cancer, with special reference to extra-intestinal malignancies, in patients with inflammatory bowel disease. World J Gastroenterol 2013; 19:9359-9365. [PMID: 24409063 PMCID: PMC3882409 DOI: 10.3748/wjg.v19.i48.9359] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2013] [Revised: 09/20/2013] [Accepted: 10/19/2013] [Indexed: 02/06/2023] Open
Abstract
AIM To determine the incidence and characteristics of intestinal and extra-intestinal cancers among patients with inflammatory bowel disease in a Spanish hospital and to compare them with those of the local population. METHODS This was a prospective, observational, 7-year follow-up, cohort study. Cumulative incidence, incidence rates based on person-years of follow-up and relative risk were calculated for patients with inflammatory bowel disease and compared with the background population. The incidence of cancer was determined using a hospital-based data registry from Hospital Universitario de Fuenlabrada. Demographic data and details about time from diagnosis of inflammatory bowel disease to occurrence of cancer, disease extent, inflammatory bowel disease treatment, cancer therapy and cancer evolution were also collected in the inflammatory bowel disease cohort. RESULTS Eighteen of 590 patients with inflammatory bowel disease developed cancer [cumulative incidence = 3% (95%CI: 1.58-4.52) vs 2% (95%CI: 1.99-2.11) in the background population; RR = 1.5; 95%CI: 0.97-2.29]. The cancer incidence among inflammatory bowel disease patients was 0.53% (95%CI: 0.32-0.84) per patient-year of follow-up. Patients with inflammatory bowel disease had a significantly increased relative risk of urothelial carcinoma (RR = 5.23, 95%CI: 1.95-13.87), appendiceal mucinous cystadenoma (RR = 36.6, 95%CI: 7.92-138.4), neuroendocrine carcinoma (RR = 13.1, 95%CI: 1.82-29.7) and rectal carcinoid (RR = 8.94, 95%CI: 1.18-59.7). Colorectal cancer cases were not found. CONCLUSION The overall risk of cancer did not significantly increase in our inflammatory bowel disease patients. However, there was an increased risk of urinary bladder cancer and, with less statistical power, an increased risk of appendiceal mucinous cystadenoma and of neuroendocrine tumors. Colorectal cancer risk was low in our series.
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Drukker L, Edden Y, Reissman P. Adenocarcinoma of the small bowel in a patient with occlusive Crohn’s disease. World J Gastrointest Oncol 2012; 4:184-6. [PMID: 22844550 PMCID: PMC3406284 DOI: 10.4251/wjgo.v4.i7.184] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2011] [Revised: 05/29/2012] [Accepted: 05/31/2012] [Indexed: 02/05/2023] Open
Abstract
A 40-year-old male, diagnosed with mild Crohn’s disease (CD) 11 years ago but with no prior abdominal surgeries, was diagnosed with a small bowel stricture, due to ongoing abdominal pain and intolerance of enteral diet, and referred for surgical treatment. Exploratory laparoscopy revealed a white solid mass causing a near total jejunal obstruction with significant proximal dilatation. An adjacent small node was sampled for frozen biopsy, revealing a lymph node infiltrated with adenocarcinoma. Laparoscopic assisted small bowel resection and appendectomy were carried out. Final pathological results supported the initial report of diffuse small bowel adenocarcinoma. In conclusion, once a small bowel stricture associated with CD is suspected, rapid action should be considered to avoid late diagnosis of a neoplasia.
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Affiliation(s)
- Lior Drukker
- Lior Drukker, Yair Edden, Petachia Reissman, Department of General Surgery, Shaare Zedek Medical Center, Hebrew University, Hadassah School of Medicine, PO Box 3235, Jerusalem 91031, Israel
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Kamiya T, Ando T, Ishiguro K, Maeda O, Watanabe O, Hibi S, Mimura S, Ujihara M, Hirayama Y, Nakamura M, Miyahara R, Ohmiya N, Goto H. Intestinal cancers occurring in patients with Crohn's disease. J Gastroenterol Hepatol 2012; 27 Suppl 3:103-7. [PMID: 22486881 DOI: 10.1111/j.1440-1746.2012.07082.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND AND AIMS The number of patients with Crohn's disease (CD) and the number of cases of intestinal cancer associated with CD have both been increasing in Japan. However, the number of reported cases is lower than for ulcerative colitis-associated cancer. The aim of this study was to identify the clinical picture of CD-associated intestinal cancer in a consecutive series of patients with CD and to stress the importance of surveillance. METHODS We enrolled 174 consecutive patients (130 men, 44 women, mean age 25 years) diagnosed with CD and investigated the development of intestinal cancer from October 1998 to July 2010. There were 104 cases of the ileocolitis type, 47 of ileitis, and 23 of colitis. RESULTS Intestinal cancer developed in two male patients (1.5% of the total), whose respective ages at onset of CD were 41 and 19 years, and 55 and 37 years at onset of cancer. Both cases were of ileocolitis-type CD; one cancer developed in the rectum and the other in the small bowel, and both were accompanied by severe stricture. Histopathological results revealed well and moderately differentiated adenocarcinoma, respectively. CONCLUSIONS Intestinal cancer developed in patients with ileocolitis-type CD of more than 10 years' duration. Our findings suggest that patients with chronic, widespread CD should be under cancer surveillance.
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Affiliation(s)
- Toru Kamiya
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Keefer L, Doerfler B, Artz C. Optimizing management of Crohn's disease within a project management framework: results of a pilot study. Inflamm Bowel Dis 2012; 18:254-60. [PMID: 21351218 PMCID: PMC3111841 DOI: 10.1002/ibd.21679] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2011] [Accepted: 01/17/2011] [Indexed: 02/06/2023]
Abstract
BACKGROUND Psychotherapy for Crohn's disease (CD) has focused on patients with psychological distress. Another approach to optimize management of CD is to target patients who do not exhibit psychological distress but engage in behaviors that undermine treatment efficacy / increase risk for flare. We sought to determine the feasibility/acceptability and estimate the effects of a program framed around Project Management (PM) principles on CD outcomes. METHODS Twenty-eight adults with quiescent CD without a history of psychiatric disorder were randomized to PM (n = 16) or treatment as usual (TAU; n = 12). Baseline and follow-up measures were Inflammatory Bowel Disease Questionnaire (IBDQ), Medication Adherence Scale (MAS), Perceived Stress Questionnaire (PSQ), and IBD Self-Efficacy Scale (IBD-SES). RESULTS There were significant group × time effects favoring PM on IBDQ-Total Score (F(1) = 15.2, P = 0.001), IBDQ-Bowel (F(1) = 6.5, P = 0.02), and IBDQ-Systemic (F(1) = 9.3, P = 0.007) but not IBDQ-Emotional (F(1) = 1.9, P = ns) or IBDQ-Social (F(1) = 2.4, P = ns). There was a significant interaction effect favoring PM with respect to PSQ (F(1) = 8.4, P = 0.01) and IBD-SES (F(1) = 12.2, P = 0.003). There was no immediate change in MAS (F(1) = 4.3, P = ns). Moderate effect sizes (d > 0.30) were observed for IBDQ total score (d = 0.45), IBDQ bowel health (d = 0.45), and systemic health (d = 0.37). Effect sizes for PSQ (d = 0.13) and IBDSES (d = 0.17) were smaller. CONCLUSIONS Behavioral programs that appeal to patients who may not seek psychotherapy for negative health behaviors may improve quality of life and potentially disease course and outcomes.
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Affiliation(s)
- Laurie Keefer
- Northwestern University, Division of Gastroenterology, Chicago, Illinois 60611, USA.
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Singh H, Nugent Z, Demers AA, Bernstein CN. Increased risk of nonmelanoma skin cancers among individuals with inflammatory bowel disease. Gastroenterology 2011; 141:1612-20. [PMID: 21806945 DOI: 10.1053/j.gastro.2011.07.039] [Citation(s) in RCA: 111] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2011] [Revised: 06/28/2011] [Accepted: 07/22/2011] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS There are limited data on the risk of nonmelanoma skin cancer (NMSC) among individuals with inflammatory bowel disease (IBD), including those with or without exposure to immunosuppressant medications. METHODS Individuals with IBD (n = 9618) were identified from the University of Manitoba IBD Epidemiology Database and matched with randomly selected controls (n = 91,378) based on age, sex, and postal area of residence on the date of IBD diagnosis (index date). Groups were followed up from the index date until a diagnosis of any invasive cancer (including NMSC), death, migration from the province, or the end of the study (December 31, 2009), whichever came first. Cox regression analysis was performed to calculate the relative risk of NMSC among the individuals with IBD, adjusting for frequency of ambulatory care visits and socioeconomic status. RESULTS Of the individuals followed, 1696 were diagnosed with basal cell skin cancer (BCC) and 341 were diagnosed with squamous cell skin cancer (SCC). Individuals with IBD had an increased risk for BCC, compared with controls (hazard ratio, 1.20; 95% confidence interval [CI], 1.03-1.40). Among patients with IBD, use of thiopurines increased the risk of SCC (hazard ratio, 5.40; 95% CI, 2.00-14.56), compared with controls. Use of thiopurines also was associated with SCC in a case-control, nested analysis of individuals with IBD (odds ratio, 20.52; 95% CI, 2.42-173.81). CONCLUSIONS The risk of BCC could be increased among individuals with IBD. Use of thiopurines increases the risk of SCC among individuals with IBD.
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Affiliation(s)
- Harminder Singh
- Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
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