|
1
|
Wang M, Gao C, Lessing DJ, Chu W. Saccharomyces cerevisiae SC-2201 Attenuates AOM/DSS-Induced Colorectal Cancer by Modulating the Gut Microbiome and Blocking Proinflammatory Mediators. Probiotics Antimicrob Proteins 2025; 17:1523-1535. [PMID: 38329696 DOI: 10.1007/s12602-024-10228-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/02/2024] [Indexed: 02/09/2024]
Abstract
Colorectal cancer is the third most common cancer in the world today, and studies have shown that the ratio of Candida to Saccharomyces cerevisiae increased, and the abundance of S. cerevisiae in the intestines of patients with colorectal cancer decreased, which suggests that there is an imbalance in the proportion of fungi in the intestines of patients with colorectal cancer. The objective of this study was to screen S. cerevisiae isolate from traditional Chinese fermentation starters and assess its ability to ameliorate dysbiosis and to alleviate the carcinogenic process of azoxymethane/dextran sodium sulfate-induced colorectal cancer in mice model. S. cerevisiae strain SC-2201 was isolated and exhibited probiotic properties, including the ability to survive in an acidic pH environment and in the presence of bile salts in the gastrointestinal tract, as well as antioxidant activities. Oral administration of S. cerevisiae SC-2201 not only alleviated weight loss but also reduced colonic shortening and histological damage in azoxymethane/dextran sodium sulfate-induced colorectal cancer in mice. Furthermore, the administration of S. cerevisiae SC-2201 suppressed the expression of proinflammatory mediators, such as interleukin-1β, interleukin-6, cyclooxygenase-2, vascular endothelial growth factor, nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3. Specifically, the analysis of gut bacteriome showed a significant decrease in Bacteroidota and Campylobacterota levels, as well as an increase in Proteobacteria level in the colorectal cancer group, which was alleviated by supplementation with S. cerevisiae SC-2201. The analysis of the mycobiome revealed a significant increase in the levels of Basidiomycota, Apiosordaria, Naganishia, and Taphrina genera in the colorectal cancer group, which were alleviated after supplementation with S. cerevisiae SC-2201. However, the levels of Xenoramularia, Entoloma, and Keissleriella were significantly increased after administration with S. cerevisiae SC-2201. Overall, the findings of this study demonstrate that S. cerevisiae SC-2201 possesses potential probiotic properties and can effectively attenuate the development of colorectal cancer, highlighting its cancer-preventive potential. This is the first report of a S. cerevisiae strain isolated from traditional Chinese fermentation starters which showed good probiotic properties, and mitigated azoxymethane/dextran sodium sulfate-induced colorectal cancer by modulating the gut microbiome and blocking proinflammatory mediators in mice.
Collapse
Affiliation(s)
- Minyu Wang
- School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Jiangsu Province, Nanjing, 210009, People's Republic of China
| | - Chongzheng Gao
- School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Jiangsu Province, Nanjing, 210009, People's Republic of China
| | - Duncan James Lessing
- School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Jiangsu Province, Nanjing, 210009, People's Republic of China
| | - Weihua Chu
- School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Jiangsu Province, Nanjing, 210009, People's Republic of China.
| |
Collapse
|
|
2
|
Angyal D, Balogh F, Bessissow T, Wetwittayakhlang P, Ilias A, Gonczi L, Lakatos PL. The Role of Histology Alongside Clinical and Endoscopic Evaluation in the Management of IBD-A Narrative Review. J Clin Med 2025; 14:2485. [PMID: 40217934 PMCID: PMC11989425 DOI: 10.3390/jcm14072485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2025] [Revised: 04/01/2025] [Accepted: 04/03/2025] [Indexed: 04/14/2025] Open
Abstract
Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory conditions requiring continuous monitoring. Today, endoscopy is the gold standard for assessing disease activity, with histological evaluation providing additional insights. Studies suggest that persistent histological inflammation, despite endoscopic remission, may be associated with a higher risk of relapse in UC, suggesting its role in treatment decisions. In CD, histological assessment is limited by its patchy nature, transmural inflammation and lack of validated scoring systems. Few retrospective studies with conflicting results have examined the prognostic value of histological remission in CD, and its role in predicting long-term outcomes remains unclear. This narrative review aims to summarize and discuss the available evidence regarding the additional value of histological assessment in IBD management. In UC, the ongoing VERDICT study is expected to provide evidence on the impact of incorporating histological remission as a treatment target compared to a strategy based on clinical and endoscopic activity. Recently published interim results indicate that targeting histological remission does not lead to better clinical/biochemical disease activity. Thus, while patients achieving histological healing are associated with better outcomes, the question arises whether achieving histological remission is an intrinsic (biological) characteristic of the patient and indicator of an easier to treat patient group or a result of more effective therapy.
Collapse
Affiliation(s)
- Dorottya Angyal
- Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (D.A.)
| | - Fruzsina Balogh
- Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (D.A.)
- Division of Gastroenterology, Central Hospital of Northern Pest, Military Hospital, 1062 Budapest, Hungary
| | - Talat Bessissow
- Division of Gastroenterology, McGill University, Montreal, QC H3A 0G4, Canada
| | - Panu Wetwittayakhlang
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai 90110, Thailand;
| | - Akos Ilias
- Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (D.A.)
| | - Lorant Gonczi
- Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (D.A.)
| | - Peter L. Lakatos
- Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (D.A.)
- Division of Gastroenterology, McGill University, Montreal, QC H3A 0G4, Canada
| |
Collapse
|
|
3
|
Ohara J, Maeda Y, Ogata N, Kuroki T, Misawa M, Kudo SE, Nemoto T, Yamochi T, Iacucci M. Automated Neutrophil Quantification and Histological Score Estimation in Ulcerative Colitis. Clin Gastroenterol Hepatol 2025; 23:846-854.e7. [PMID: 39059545 DOI: 10.1016/j.cgh.2024.06.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 06/27/2024] [Accepted: 06/27/2024] [Indexed: 07/28/2024]
Abstract
BACKGROUND In the management of ulcerative colitis (UC), histological remission is increasingly recognized as the ultimate goal. The absence of neutrophil infiltration is crucial for assessing remission. This study aimed to develop an artificial intelligence (AI) system capable of accurately quantifying and localizing neutrophils in UC biopsy specimens to facilitate histological assessment. METHODS Our AI system, which incorporates semantic segmentation and object detection models, was developed to identify neutrophils in hematoxylin and eosin-stained whole slide images. The system assessed the presence and location of neutrophils within either the epithelium or lamina propria and predicted components of the Nancy Histological Index and the PICaSSO Histologic Remission Index. We evaluated the system's performance against that of experienced pathologists and validated its ability to predict future clinical relapse risk in patients with clinically remitted UC. The primary outcome measure was the clinical relapse rate, defined as a partial Mayo score of ≥3. RESULTS The model accurately identified neutrophils, achieving a performance of 0.77, 0.81, and 0.79 for precision, recall, and F-score, respectively. The system's histological score predictions showed a positive correlation with the pathologists' diagnoses (Spearman's ρ = 0.68-0.80; P < .05). Among patients who relapsed, the mean number of neutrophils in the rectum was higher than in those who did not relapse. Furthermore, the study highlighted that higher AI-based PICaSSO Histologic Remission Index and Nancy Histological Index scores were associated with hazard ratios increasing from 3.2 to 5.0 for evaluating the risk of UC relapse. CONCLUSIONS The AI system's precise localization and quantification of neutrophils proved valuable for histological assessment and clinical prognosis stratification.
Collapse
Affiliation(s)
- Jun Ohara
- Department of Pathology, Showa University School of Medicine, Tokyo, Japan.
| | - Yasuharu Maeda
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan; APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland
| | - Noriyuki Ogata
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Takanori Kuroki
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Masashi Misawa
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Shin-Ei Kudo
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Tetsuo Nemoto
- Department of Diagnostic Pathology, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Toshiko Yamochi
- Department of Pathology, Showa University School of Medicine, Tokyo, Japan
| | - Marietta Iacucci
- APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland
| |
Collapse
|
|
4
|
Liang RFH, Lin H, Chau CYP, Lim WC. Histologic healing and clinical outcomes in ulcerative colitis. Intest Res 2025; 23:182-192. [PMID: 39295311 PMCID: PMC12081077 DOI: 10.5217/ir.2024.00058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Revised: 06/30/2024] [Accepted: 07/22/2024] [Indexed: 09/21/2024] Open
Abstract
BACKGROUND/AIMS Growing evidence suggests histologic healing (HH) improves clinical outcomes in ulcerative colitis (UC) patients beyond endoscopic healing (EH). We hypothesize that HH is associated with better clinical outcomes in Asian UC patients, for whom data is lacking. METHODS We performed a retrospective study of UC patients in clinical remission (CR) with a follow-up colonoscopy and minimum 1-year follow-up post-colonoscopy. Primary outcome was clinical relapse (CRL), defined as either a Simple Clinical Colitis Activity Index score of > 2, medication escalation, hospitalization or colectomy. Predictors of CRL and HH were assessed. RESULTS One hundred patients were included with a median follow-up of 22 months. At index colonoscopy, 80 patients were in EH. On follow-up, 41 patients experienced CRL. Of 80 patients in EH, 34 (42.5%) had persistent histologic activity (Nancy Index ≥ 2) and 29 (36.3%) relapsed during the follow-up period. Amongst patients in CR and EH, those with HH had lower CRL rate (26.1% vs. 50.0%, P= 0.028) and longer CRL-free survival (mean 46.1 months vs. 31.5 months, P= 0.015) than those with persistent histologic activity. On bivariable analysis of 100 patients in CR, HH, and Mayo endoscopic score (MES) of 0 were significantly associated with lower risk of CRL. On multivariable analysis, only MES 0 remained predictive of lower CRL risk. CONCLUSIONS Above and beyond CR and EH, achieving HH improves clinical outcomes in Asian UC patients. However, HH may not confer incremental benefit if MES 0 has been achieved. Further prospective studies evaluating the benefit of histologically guided therapeutic decisions are needed.
Collapse
Affiliation(s)
| | - Huiyu Lin
- Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, Singapore
| | | | - Wee Chian Lim
- Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, Singapore
| |
Collapse
|
|
5
|
Couto Sousa D, Fernandes SR, Bernardo S, Correia L, Cortez-Pinto H, Magro F. Treat-to-Target in Inflammatory Bowel Disease: An Updated Survey of Treatment Strategies among Portuguese Gastroenterologists. GE - PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2024:1-8. [DOI: 10.1159/000541867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Background: In 2018, the authors surveyed the clinical practices among Portuguese gastroenterologists (PGEs) regarding treatment targets in Crohn’s disease (CD) and ulcerative colitis (UC). Since then, new evidence has emerged supporting additional targets, such as transmural remission and histological remission. This study provides an updated assessment of treatment practices among PGE with special emphasis on these new targets. Methods: Using the Portuguese Inflammatory bowel disease Study Group (GEDII) physician database, we invited PGE to participate in an anonymous online survey. Results: Fifty-six physicians agreed to participate in the study. Deep remission, steroid-free clinical remission, endoscopic remission, and biomarker remission were ranked among the most important treatment targets in CD (89%, 80%, 89%, and 84%, respectively) and UC (82%, 84%, 79%, and 84%, respectively). In CD, transmural remission was considered a target by 70% of participants, with 48% agreeing to intensify treatment to achieve it. In UC, histological remission was aimed by only 45% of PGE with most (88%) being unwilling to intensify treatment to achieve this goal. Physicians were more likely to seek endoscopic remission in CD and UC in younger and healthier patients, compared to older patients with comorbidities. Conclusion: PGEs are increasingly pursuing tougher treatment targets such as transmural remission in CD and, to a lesser extent, histological remission in UC. Physicians are more willing to escalate treatment to achieve endoscopic remission in younger patients.
Collapse
|
|
6
|
Abbas A, Di Fonzo DMP, Wetwittayakhlang P, Al-Jabri R, Lakatos PL, Bessissow T. Management of ulcerative colitis: where are we at and where are we heading? Expert Rev Gastroenterol Hepatol 2024; 18:567-574. [PMID: 39470444 DOI: 10.1080/17474124.2024.2422370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Revised: 10/14/2024] [Accepted: 10/24/2024] [Indexed: 10/30/2024]
Abstract
INTRODUCTION Remission rates for ulcerative colitis (UC) remain low despite significant progress in disease understanding and the introduction of novel therapeutic agents. Several challenges contribute to this, including the heterogeneity of the disease, suboptimal efficacy of current diagnostic and therapeutic tools, drug safety concerns, and limited access to newer treatment options. AREAS COVERED This review evaluates current treatment targets in UC, assessing the effectiveness of various therapies and management strategies in achieving remission. We explore the potential role of personalized medicine, which tailors treatment based on clinical predictors, genetic factors, and immunologic profiles. Personalized approaches show promise in improving remission rates by addressing the unique characteristics of each patient. We also discussed the feasibility of adapting such management models and suggested solutions to some of the challenges in their implementation. EXPERT OPINION Future efforts should prioritize the continued development of biologics, small molecules, and digital health solutions, alongside noninvasive monitoring techniques. These innovations could not only enhance patient outcomes by improving remission rates but also reduce healthcare costs by minimizing hospitalization and surgical interventions. Ultimately, a personalized, stratified approach to UC management is key to optimizing patient care and addressing the unmet needs in this field.
Collapse
Affiliation(s)
- Adnan Abbas
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University, Health Centre, Montreal, Canada
| | - David M P Di Fonzo
- Department of Medicine, McGill University Health Centre, Montreal, Canada
| | - Panu Wetwittayakhlang
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University, Health Centre, Montreal, Canada
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
| | - Reem Al-Jabri
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University, Health Centre, Montreal, Canada
| | - Peter L Lakatos
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University, Health Centre, Montreal, Canada
- Department of Medicine, Semmelweis University, Budapest, Hungary
| | - Talat Bessissow
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University, Health Centre, Montreal, Canada
| |
Collapse
|
|
7
|
Feakins RM. Inflammatory disorders of the large intestine. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:709-857. [DOI: 10.1002/9781119423195.ch35] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
8
|
Herrlinger KR, Stange EF. To STRIDE or not to STRIDE: a critique of "treat to target" in ulcerative colitis. Expert Rev Gastroenterol Hepatol 2024; 18:493-504. [PMID: 39193775 DOI: 10.1080/17474124.2024.2397654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 08/24/2024] [Indexed: 08/29/2024]
Abstract
INTRODUCTION The STRIDE consensus intends to complement the clinical endpoint with an endoscopic endpoint of mucosal healing and others as treatment targets in ulcerative colitis. If these targets are not reached, STRIDE requires dose or timing adjustments or switching the medication. This narrative review provides a critique of this concept. AREAS COVERED We analyze and discuss the limitations of current endpoints as targets, their currently limited achievability, and the lacking evidence from controlled trials relating to 'treat to target.' The relevant publications in PubMed were identified in a literature review with the key word 'ulcerative colitis.' EXPERT OPINION In ulcerative colitis, the standard clinical target is measured traditionally by the MAYO-score, but in variable combinations of patient and physician reported outcomes as well as also different definitions of the endoscopic part. Only a score of 0 is more stringent than clinical remission but is only achieved by a minority of patients in first and even less in second line therapy. The concept is not based on clear evidence that patients indeed benefit from appropriate escalation of treatment. Until the STRIDE approach is proven to be superior to standard treatment focusing on clinical well-being, the field should remain reluctant.
Collapse
Affiliation(s)
| | - Eduard F Stange
- Innere Medizin I, UniversitätsklinikTübingen, Tübingen, Germany
| |
Collapse
|
|
9
|
Fanizza J, Bencardino S, Allocca M, Furfaro F, Zilli A, Parigi TL, Fiorino G, Peyrin-Biroulet L, Danese S, D'Amico F. Inflammatory Bowel Disease and Colorectal Cancer. Cancers (Basel) 2024; 16:2943. [PMID: 39272800 PMCID: PMC11394070 DOI: 10.3390/cancers16172943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 08/21/2024] [Accepted: 08/22/2024] [Indexed: 09/15/2024] Open
Abstract
Patients with inflammatory bowel diseases (IBDs), including both ulcerative colitis (UC) and Crohn's disease (CD), are at a higher risk of developing colorectal cancer (CRC). However, advancements in endoscopic imaging techniques, integrated surveillance programs, and improved medical therapies have led to a decrease in the incidence of CRC among IBD patients. Currently, the management of patients with IBD who have a history of or ongoing active malignancy is an unmet need. This involves balancing the risk of cancer recurrence/progression with the potential exacerbation of IBD if the medications are discontinued. The objective of this review is to provide an updated summary of the epidemiology, causes, risk factors, and surveillance approaches for CRC in individuals with IBD, and to offer practical guidance on managing IBD patients with history of previous or active cancer.
Collapse
Affiliation(s)
- Jacopo Fanizza
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Sarah Bencardino
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Federica Furfaro
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Alessandra Zilli
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Tommaso Lorenzo Parigi
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Gionata Fiorino
- IBD Unit, Department of Gastroenterology and Digestive Endoscopy, San Camillo-Forlanini Hospital, 00152 Rome, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- INSERM, NGERE, University of Lorraine, F-54000 Nancy, France
- INFINY Institute, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- FHU-CURE, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- Groupe Hospitalier Privè Ambroise Parè-Hartmann, Paris IBD Center, 92200 Neuilly sur Seine, France
- Division of Gastroenterology and Hepatology, McGill University Health Center, Montreal, QC H4A 3J1, Canada
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Ferdinando D'Amico
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| |
Collapse
|
|
10
|
Zhang Y, Chu X, Wang L, Yang H. Global patterns in the epidemiology, cancer risk, and surgical implications of inflammatory bowel disease. Gastroenterol Rep (Oxf) 2024; 12:goae053. [PMID: 38984068 PMCID: PMC11233070 DOI: 10.1093/gastro/goae053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 04/10/2024] [Accepted: 04/22/2024] [Indexed: 07/11/2024] Open
Abstract
Inflammatory bowel disease (IBD), mainly including ulcerative colitis and Crohn's disease, imposes a huge medical and economic burden worldwide. Recently, the diagnosis, treatment, and surveillance of IBD have advanced rapidly, which has changed the epidemiology, cancer risk, and surgery risk of IBD. Here, we reviewed the recent literature on the epidemiology, IBD-related cancer, and IBD-related surgery. We created a choropleth map to show the worldwide incidence trend for Crohn's disease and ulcerative colitis. We also found that the cancer risk and surgery risk of IBD are declining and discussed some risk factors associated with them. Based on the recent trend, we proposed several suggestions and hoped to reduce the global burden of IBD as far as possible.
Collapse
Affiliation(s)
- Yiming Zhang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, P. R. China
| | - Xiaotian Chu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, P. R. China
| | - Li Wang
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences; School of Basic Medicine Peking Union Medical College, Beijing, P. R. China
| | - Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, P. R. China
| |
Collapse
|
|
11
|
She T, Ren S, He H, Symer M, Katz S. Ulcerative Colitis or Not? A Case of Dysplasia, Gastrointestinal Bleeding, and Juvenile Polyposis in a 27-Year-Old Man. ACG Case Rep J 2024; 11:e01450. [PMID: 39035206 PMCID: PMC11259387 DOI: 10.14309/crj.0000000000001450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Accepted: 06/24/2024] [Indexed: 07/23/2024] Open
Abstract
Juvenile polyposis syndrome lies within the family of hamartomatous polyposis syndromes characterized by polyps that appear benign but harbor an increased risk of colorectal and gastric cancer. This 27-year-old man with severe ulcerative colitis was discovered to have concomitant juvenile polyposis syndrome during diagnostic workup for gastrointestinal bleeding. The implications of this rare association complicate both diagnostic and treatment modalities since both diseases confer an increased risk of cancer.
Collapse
Affiliation(s)
- Tianyu She
- Department of Medicine, New York University Langone Long Island, New York, NY
| | - Stephanie Ren
- Department of Medicine, New York University Langone Long Island, New York, NY
| | - Harry He
- Department of Gastroenterology, New York University Langone Long Island, New York, NY
| | - Matthew Symer
- Department of Surgery, New York University Langone Long Island, New York, NY
| | - Seymour Katz
- Division of Gastroenterology and Hepatology, New York University Langone Medical Center, New York, NY
| |
Collapse
|
|
12
|
Maeda Y, Kudo SE, Santacroce G, Ogata N, Misawa M, Iacucci M. Artificial intelligence-assisted colonoscopy to identify histologic remission and predict the outcomes of patients with ulcerative colitis: A systematic review. Dig Liver Dis 2024; 56:1119-1125. [PMID: 38643020 DOI: 10.1016/j.dld.2024.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 03/11/2024] [Accepted: 04/04/2024] [Indexed: 04/22/2024]
Abstract
This systematic review evaluated the current status of AI-assisted colonoscopy to identify histologic remission and predict the clinical outcomes of patients with ulcerative colitis. The use of artificial intelligence (AI) has increased substantially across several medical fields, including gastrointestinal endoscopy. Evidence suggests that it may be helpful to predict histologic remission and relapse, which would be beneficial because current histological diagnosis is limited by the inconvenience of obtaining biopsies and the high cost and time-intensiveness of pathological diagnosis. MEDLINE and the Cochrane Central Register of Controlled Trials were searched for studies published between January 1, 2000, and October 31, 2023. Nine studies fulfilled the selection criteria and were included; five evaluated the prediction of histologic remission, two assessed the prediction of clinical outcomes, and two evaluated both. Seven were prospective observational or cohort studies, while two were retrospective observational studies. No randomized controlled trials were identified. AI-assisted colonoscopy demonstrated sensitivity between 65 %-98 % and specificity values of 80 %-97 % for identifying histologic remission. Furthermore, it was able to predict future relapse in patients with ulcerative colitis. However, several challenges and barriers still exist to its routine clinical application, which should be overcome before the true potential of AI-assisted colonoscopy can be fully realized.
Collapse
Affiliation(s)
- Yasuharu Maeda
- Digestive Disease Center, Showa University Northern Yokohama Hospital, 35-1 Chigasaki-chuo, Tsuzuki, Yokohama 224-8503, Japan; APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, T12 YT20, Ireland.
| | - Shin-Ei Kudo
- Digestive Disease Center, Showa University Northern Yokohama Hospital, 35-1 Chigasaki-chuo, Tsuzuki, Yokohama 224-8503, Japan
| | - Giovanni Santacroce
- APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, T12 YT20, Ireland
| | - Noriyuki Ogata
- Digestive Disease Center, Showa University Northern Yokohama Hospital, 35-1 Chigasaki-chuo, Tsuzuki, Yokohama 224-8503, Japan
| | - Masashi Misawa
- Digestive Disease Center, Showa University Northern Yokohama Hospital, 35-1 Chigasaki-chuo, Tsuzuki, Yokohama 224-8503, Japan
| | - Marietta Iacucci
- APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, T12 YT20, Ireland
| |
Collapse
|
|
13
|
Picardo S, Venugopal K, Cheng W, Ragunath K. Adherence to endoscopic surveillance guidelines for patients with inflammatory bowel disease: An Australian cohort study. J Gastroenterol Hepatol 2024; 39:506-511. [PMID: 38069495 DOI: 10.1111/jgh.16438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 11/05/2023] [Accepted: 11/14/2023] [Indexed: 03/05/2024]
Abstract
BACKGROUND AND AIM Patients with inflammatory bowel disease have an increased risk of developing colorectal cancer as compared with the general population. Endoscopic surveillance to detect early dysplastic changes is advised by several published clinical guidelines, which provide recommendations as to the timing and performance of surveillance procedures. There is a paucity of data as to adherence with these guidelines in clinical practice. METHODS A longitudinal inception cohort study of all new patients diagnosed with inflammatory bowel disease across a service network of Australian hospitals between January 2005 and June 2014, with continuous follow-up in a gastroenterology clinic until December 31, 2022. Patients were included if they warranted surveillance according to the Australian guidelines. Adherence to guidelines and technical and quality measures were reported. RESULTS A total of 136 patients were included, and a total of 263 surveillance procedures were performed. Ninety-five patients (70%) had their first surveillance colonoscopy within the correct time interval. Fifty patients (37%) were completely adherent to guidelines with respect to timing of all surveillance procedure. The overall dysplasia detection rate for surveillance procedures was 10%. Chromoendoscopy was only performed in 16% of procedures. CONCLUSIONS Adherence to endoscopic surveillance guidelines with regard to timing of procedures and the utilization of chromoendoscopy is poor. Further clinician education, promotion of the surveillance guidelines and incorporation of chromoendoscopy training as part of the national colonoscopy training program may improve adherence to guidelines.
Collapse
Affiliation(s)
- Sherman Picardo
- Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Western Australia, Australia
- Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia
| | - Kannan Venugopal
- Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Western Australia, Australia
| | - Wendy Cheng
- Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Western Australia, Australia
- Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia
| | - Krish Ragunath
- Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Western Australia, Australia
- Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia
| |
Collapse
|
|
14
|
Elford AT, Hirsch R, McKay OM, Browne M, Moore GT, Bell S, Swan M. Identifying the real-world challenges of dysplasia surveillance in inflammatory bowel disease: a retrospective cohort study in a tertiary health network. Intern Med J 2024; 54:96-103. [PMID: 37093665 DOI: 10.1111/imj.16102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 04/12/2023] [Indexed: 04/25/2023]
Abstract
BACKGROUND Dysplasia surveillance in inflammatory bowel disease (IBD) is often suboptimal and deviates from guidelines. AIMS To assess dysplasia surveillance behaviours and adherence to guidelines amongst a large tertiary teaching health network with a specialised IBD unit to identify areas where dysplasia surveillance could be improved. METHODS A retrospective audit of IBD surveillance colonoscopy practice over an 18-month period was performed using the Provation Endoscopy Database and the hospital's primary sclerosing cholangitis database. RESULTS The audit identified 115 dysplasia surveillance colonoscopies. A total of 37% of index dysplasia colonoscopies were outside recommended guidelines. A total of 10% had inadequate bowel preparation and only 40% had excellent bowel preparation. A total of 28% of patients underwent dye-based chromoendoscopy and 69% underwent high-definition white-light endoscopy. Dye chromoendoscopy was more likely to be used by IBD specialists than interventional endoscopists (P = 0.008) and other endoscopists (P = 0.004). Only IBD specialists and interventional endoscopists used dye chromoendoscopy. Dysplasia or colorectal cancer was detected in 3.4% of the colonoscopies. Overall, the several dysplasia examinations were lower than expected. CONCLUSIONS Dysplasia surveillance in the IBD population remains an area of improvement given the current national guidelines. IBD specialists are more likely to perform dye chromoendoscopy than other endoscopists/gastroenterologists. Dysplasia rates in this real-world contemporary setting are less than expected in historical studies and may represent improvements in IBD management principles and medications.
Collapse
Affiliation(s)
- Alexander T Elford
- Monash Health, Melbourne, Victoria, Australia
- The University of Melbourne, Melbourne, Victoria, Australia
| | - Ryan Hirsch
- Monash Health, Melbourne, Victoria, Australia
| | | | | | - Gregory T Moore
- Monash Health, Melbourne, Victoria, Australia
- Monash University, Melbourne, Victoria, Australia
| | - Sally Bell
- Monash Health, Melbourne, Victoria, Australia
- Monash University, Melbourne, Victoria, Australia
| | - Michael Swan
- Monash Health, Melbourne, Victoria, Australia
- Monash University, Melbourne, Victoria, Australia
| |
Collapse
|
|
15
|
Jucan AE, Gavrilescu O, Dranga M, Popa IV, Mihai IR, Mihai VC, Stefanescu G, Drug VL, Prelipcean CC, Vulpoi RA, Barboi OB, Ciortescu I, Mihai C. Evaluation of Disease Activity in Inflammatory Bowel Disease: Diagnostic Tools in the Assessment of Histological Healing. Biomedicines 2023; 11:3090. [PMID: 38002090 PMCID: PMC10669373 DOI: 10.3390/biomedicines11113090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 11/10/2023] [Accepted: 11/15/2023] [Indexed: 11/26/2023] Open
Abstract
Inflammatory bowel disease (IBD) comprises two types of chronic intestinal disorders: Crohn's disease and ulcerative colitis. In long-standing ulcerative colitis disease activity, histological persistent inflammation has been linked to an increased risk of relapse, and long-term corticosteroid use, even when endoscopic remission is reached. In Crohn's disease, the discontinuous nature of lesions and transmural inflammation have limited the standardized histological assessment. The current evidence from research proposes that besides clinical and endoscopic healing, the achievement of histological healing constitutes an endpoint to assess disease activity and remission in IBD patients concerning better long-term disease outcomes. Histological alterations may persist even in the absence of endoscopic lesions. For these reasons, new advanced techniques promise to revolutionize the field of IBD by improving the endoscopic and histologic assessment, disease characterization, and ultimately patient care, with an established role in daily practice for objective assessment of lesions. This review outlines the importance of including microscopic evaluation in IBD, highlighting the clinical benefits of a deep state of disease remission using validated diagnostic methods and scoring systems for daily clinical practice.
Collapse
Affiliation(s)
- Alina Ecaterina Jucan
- Department of Gastroenterology, Saint Spiridon County Hospital, 700111 Iasi, Romania; (O.G.); (G.S.); (V.L.D.); (C.C.P.); (O.-B.B.); (I.C.); (C.M.)
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.V.P.); (R.-A.V.)
| | - Otilia Gavrilescu
- Department of Gastroenterology, Saint Spiridon County Hospital, 700111 Iasi, Romania; (O.G.); (G.S.); (V.L.D.); (C.C.P.); (O.-B.B.); (I.C.); (C.M.)
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.V.P.); (R.-A.V.)
| | - Mihaela Dranga
- Department of Gastroenterology, Saint Spiridon County Hospital, 700111 Iasi, Romania; (O.G.); (G.S.); (V.L.D.); (C.C.P.); (O.-B.B.); (I.C.); (C.M.)
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.V.P.); (R.-A.V.)
| | - Iolanda Valentina Popa
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.V.P.); (R.-A.V.)
| | - Ioana-Ruxandra Mihai
- Department of Rheumatology and Rehabilitation, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
| | - Vasile-Claudiu Mihai
- Department of Radiology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
| | - Gabriela Stefanescu
- Department of Gastroenterology, Saint Spiridon County Hospital, 700111 Iasi, Romania; (O.G.); (G.S.); (V.L.D.); (C.C.P.); (O.-B.B.); (I.C.); (C.M.)
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.V.P.); (R.-A.V.)
| | - Vasile Liviu Drug
- Department of Gastroenterology, Saint Spiridon County Hospital, 700111 Iasi, Romania; (O.G.); (G.S.); (V.L.D.); (C.C.P.); (O.-B.B.); (I.C.); (C.M.)
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.V.P.); (R.-A.V.)
| | - Cristina Cijevschi Prelipcean
- Department of Gastroenterology, Saint Spiridon County Hospital, 700111 Iasi, Romania; (O.G.); (G.S.); (V.L.D.); (C.C.P.); (O.-B.B.); (I.C.); (C.M.)
| | - Radu-Alexandru Vulpoi
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.V.P.); (R.-A.V.)
| | - Oana-Bogdana Barboi
- Department of Gastroenterology, Saint Spiridon County Hospital, 700111 Iasi, Romania; (O.G.); (G.S.); (V.L.D.); (C.C.P.); (O.-B.B.); (I.C.); (C.M.)
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.V.P.); (R.-A.V.)
| | - Irina Ciortescu
- Department of Gastroenterology, Saint Spiridon County Hospital, 700111 Iasi, Romania; (O.G.); (G.S.); (V.L.D.); (C.C.P.); (O.-B.B.); (I.C.); (C.M.)
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.V.P.); (R.-A.V.)
| | - Catalina Mihai
- Department of Gastroenterology, Saint Spiridon County Hospital, 700111 Iasi, Romania; (O.G.); (G.S.); (V.L.D.); (C.C.P.); (O.-B.B.); (I.C.); (C.M.)
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.V.P.); (R.-A.V.)
| |
Collapse
|
|
16
|
Jamil OK, Shaw D, Deng Z, Dinardi N, Fillman N, Khanna S, Krugliak Cleveland N, Sakuraba A, Weber CR, Cohen RD, Dalal S, Jabri B, Rubin DT, Pekow J. Inflammation in the proximal colon is a risk factor for the development of colorectal neoplasia in inflammatory bowel disease patients with primary sclerosing cholangitis. Therap Adv Gastroenterol 2023; 16:17562848231184985. [PMID: 37692199 PMCID: PMC10486214 DOI: 10.1177/17562848231184985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Accepted: 06/12/2023] [Indexed: 09/12/2023] Open
Abstract
Background Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) have an increased risk of developing colorectal neoplasia (CRN) in the proximal colon. Objectives To evaluate whether duration and severity of inflammation are linked to the development of CRN in this population. Design Retrospective, case-control chart review of patients with PSC and IBD at a tertiary care center. Methods Disease activity was scored per colonic segment at each colonoscopy prior to the first instance of observed CRN using a modified Mayo endoscopic sub-score and histologic assessment. Patients in the CRN-positive group were compared to controls that did not. Results In all, 72 PSC-IBD patients with no history of CRN were identified, 13 of whom developed CRN after at least one colonoscopy at our institution. Patients in the CRN-positive group had significantly more endoscopic (p < 0.01) and histologic (p < 0.01) inflammation in the right compared to the control group prior to the development of dysplasia. There was significantly greater endoscopic inflammation in the segment of the colon with a dysplastic lesion than other segments of the colon (p = 0.018). Patients with moderate/severe lifetime endoscopic (p = 0.02) or histologic inflammation (p = 0.04) score had a lower probability of remaining free of dysplasia during follow-up. Nearly half of the patients with dysplasia had invisible lesions found on random biopsy. Conclusions Endoscopic and histologic inflammation in the proximal colon are risk factors for CRN in patients with PSC-IBD. PSC-IBD patients frequently have subclinical inflammation, and these findings support the practice of regular assessment of disease activity and random biopsy of inflamed and uninflamed areas in patients with PSC with the goal of reducing inflammation to prevent the development of CRN.
Collapse
Affiliation(s)
- Omar K. Jamil
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Dustin Shaw
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA Digestive Diseases Research Core Center, University of Chicago Medicine, Chicago, IL, USA
| | - Zifeng Deng
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Nicholas Dinardi
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Natalie Fillman
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Shivani Khanna
- Department of Allergy and Immunology, Johns Hopkins University, Baltimore, MD, USA
| | | | - Atsushi Sakuraba
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | | | - Russell D. Cohen
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Sushila Dalal
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Bana Jabri
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA Digestive Diseases Research Core Center, University of Chicago Medicine, Chicago, IL, USA
| | - David T. Rubin
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Joel Pekow
- Inflammatory Bowel Disease Center, University of Chicago Medicine, 900 East 57th Street, MB #9, Chicago, IL 60637, USA
| |
Collapse
|
|
17
|
Sato Y, Tsujinaka S, Miura T, Kitamura Y, Suzuki H, Shibata C. Inflammatory Bowel Disease and Colorectal Cancer: Epidemiology, Etiology, Surveillance, and Management. Cancers (Basel) 2023; 15:4154. [PMID: 37627182 PMCID: PMC10452690 DOI: 10.3390/cancers15164154] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 07/13/2023] [Accepted: 08/16/2023] [Indexed: 08/27/2023] Open
Abstract
Patients with inflammatory bowel diseases (IBDs), such as ulcerative colitis and Crohn's disease, have an increased risk of developing colorectal cancer (CRC). Although advancements in endoscopic imaging techniques, integrated surveillance programs, and improved medical therapies have contributed to a decreased incidence of CRC in patients with IBD, the rate of CRC remains higher in patients with IBD than in individuals without chronic colitis. Patients with IBD-related CRCs exhibit a poorer prognosis than those with sporadic CRCs, owing to their aggressive histological characteristics and lower curative resection rate. In this review, we present an updated overview of the epidemiology, etiology, risk factors, surveillance strategies, treatment recommendations, and prognosis of IBD-related CRCs.
Collapse
Affiliation(s)
| | - Shingo Tsujinaka
- Division of Gastroenterological Surgery, Department of Surgery, Tohoku Medical and Pharmaceutical University, Sendai 983-8536, Japan
| | | | | | | | | |
Collapse
|
|
18
|
Jiang W, Lu M, Zhang L, Xu C, Wang R, Xu Y, Tang W, Zhang H. Optimizing individualized management of patients with ulcerative colitis: Identification of risk factors predicting ulcerative colitis-associated neoplasia. Medicine (Baltimore) 2023; 102:e34729. [PMID: 37565846 PMCID: PMC10419420 DOI: 10.1097/md.0000000000034729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 07/21/2023] [Indexed: 08/12/2023] Open
Abstract
The risk of developing colorectal neoplasia in patients with ulcerative colitis (UC) is increased. The purpose of this study is to analyze the risk factors of UC-associated neoplasia (UCAN) in UC patients and establish a clinical prediction model. 828 UC patients were included in this retrospective study. 602 patients were in discovery cohort and 226 patients were in validation cohort (internal validation cohort/external validation cohort: 120/106). Clinical and endoscopic data were collected. The discovery cohort was divided into UC group and UCAN group for univariate and multivariate binary logistic analyses. The UCAN clinical prediction model was established and verified. In the univariate analysis, 7 risk factors were related to UCAN. Multivariate logistic regression analysis showed that age at diagnosis of UC (OR: 1.018, 95% CI: 1.003-1.033), Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score (OR: 1.823, 95% CI: 1.562-2.128), and size of polyps (size1: OR: 6.297, 95% CI: 3.669-10.809; size2: OR: 12.014, 95% CI: 6.327-22.814) were independent risk factors of UCAN. A mathematical equation was established. The area under the ROC curve (AUC) of this model was calculated to be 0.845 (95%CI: 0.809-0.881). The sensitivity was 0.884 and the specificity was 0.688. The AUC of internal validation cohort was 0.901 (95%CI: 0.815, 0.988), sensitivity was 75.0% and specificity was 92.6%. The AUC of external validation cohort was 0.842 (95%CI: 0.709, 0.976), sensitivity was 62.5% and specificity was 93.9%. This prediction model is simple, practical, and effective for predicting the risk of UCAN, which is beneficial to the individualized management of patients with UC.
Collapse
Affiliation(s)
- Wenyu Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Meijiao Lu
- Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Li Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Chenjing Xu
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Ruohan Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Ying Xu
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Wen Tang
- Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Hongjie Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| |
Collapse
|
|
19
|
Novak G, Sever N, Hanžel J, Koželj M, Kurent T, Smrekar N, Drobne D, Zidar N. Biopsies from ulcer edge yield higher histological activity scores than biopsies from non-ulcerated mucosa in active ulcerative colitis. Eur J Gastroenterol Hepatol 2023; 35:553-558. [PMID: 36966764 DOI: 10.1097/meg.0000000000002543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/30/2023]
Abstract
BACKGROUND The appropriate location for biopsy collection in ulcerative colitis is unknown. OBJECTIVES We aimed to determine the location for biopsy collection in the presence of ulcers which yields the highest histopathological score. DESIGN AND METHODS This prospective cross-sectional study enrolled patients with ulcerative colitis and ulcers in the colon. Biopsy specimens were obtained at the edge of the ulcer; at a distance of one open forceps (7-8 mm) from the ulcer edge; at a distance of three open forceps (21-24 mm) from the ulcer edge; further referred to as locations 1, 2 and 3 respectively. Histological activity was assessed using Robarts Histopathology Index and the Nancy Histological Index. Statistical analysis was performed using mixed effects models. RESULTS A total of 19 patients were included. Decreasing trends with distance from the ulcer edge ( P < 0.0001) were observed. Biopsies procured from the edge of the ulcer (location 1) yielded a higher histopathological score compared to biopsies procured at locations 2 and 3 ( P ≤ 0.001). CONCLUSION Biopsies from the ulcer edge yield higher histopathological scores than biopsies next to the ulcer. In clinical trials with histological endpoints, biopsies should be obtained from the ulcer edge (if ulcers are present) to reliably assess histological disease activity.
Collapse
Affiliation(s)
- Gregor Novak
- Department of Gastroenterology, University Medical Centre Ljubljana
- Medical Faculty Ljubljana
| | - Nejc Sever
- Department of Gastroenterology, University Medical Centre Ljubljana
| | - Jurij Hanžel
- Department of Gastroenterology, University Medical Centre Ljubljana
- Medical Faculty Ljubljana
| | - Matic Koželj
- Department of Gastroenterology, University Medical Centre Ljubljana
| | - Tina Kurent
- Department of Gastroenterology, University Medical Centre Ljubljana
| | - Nataša Smrekar
- Department of Gastroenterology, University Medical Centre Ljubljana
| | - David Drobne
- Department of Gastroenterology, University Medical Centre Ljubljana
- Medical Faculty Ljubljana
| | - Nina Zidar
- Medical Faculty Ljubljana
- Institute of Pathology, Medical Faculty Ljubljana, University of Ljubljana, Ljubljana, Slovenia
| |
Collapse
|
|
20
|
Boulagnon-Rombi C, Marchal A, Lirsac M, Svrcek M. [Inflammatory bowel diseases: Scoring and pathological reports optimization]. Ann Pathol 2023:S0242-6498(23)00083-4. [PMID: 37059601 DOI: 10.1016/j.annpat.2023.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/13/2023] [Accepted: 03/26/2023] [Indexed: 04/16/2023]
Abstract
The two main forms of inflammatory bowel disease (IBD) are ulcerative colitis (UC) and Crohn's disease (CD). Both diseases have inflammatory flare-ups that alternate with periods of remission. The pathologist may examine biopsies of the digestive tract from IBD patients in different contexts: at the time of the initial diagnosis, in the event of a disease flare-up in order to differentiate a flare of the disease from another cause, particularly an infectious one, and during the long term follow-up of the disease in order to detect the occurrence of dysplastic lesions. Pathologists are increasingly involved in the evaluation of inflammatory activity during the follow-up of IBD patients. The therapeutic management of IBD has evolved significantly and the emergence of new treatments allows a global approach targeting endoscopic mucosal healing. However, mucosal healing is not always correlated with histological healing. Numerous studies have shown the value of histological evaluation during follow-up. A higher score for histological activity in ulcerative colitis predicts a higher likelihood of neoplasia. Histological activity is a better predictor than endoscopic inflammation of the risk. In UC, histological remission may be a long-term therapeutic goal but its role in CD remains unclear. Different scores have been developed to quantify the inflammatory activity of IBD patients and the response to treatment. The aim of this review is to present the main activity scores used in the follow-up of IBD, their interest, their evaluation and their limitations.
Collapse
Affiliation(s)
- Camille Boulagnon-Rombi
- Service de pathologie, CHU de Reims, 51092 Reims, France; CNRS, MEDyC UMR 7369, université de Reims Champagne Ardenne, 51097 Reims, France.
| | - Aude Marchal
- Émile-Gallé groupe, centre de pathologie, Nancy, France
| | | | - Magali Svrcek
- Université de la Sorbonne, Paris, France; Service d'anatomie et cytologie pathologiques, Sorbonne université, hôpital Saint-Antoine, AP-HP, Paris, France
| |
Collapse
|
|
21
|
Collard MK, Tourneur-Marsille J, Uzzan M, Albuquerque M, Roy M, Dumay A, Freund JN, Hugot JP, Guedj N, Treton X, Panis Y, Ogier-Denis E. The Appendix Orchestrates T-Cell Mediated Immunosurveillance in Colitis-Associated Cancer. Cell Mol Gastroenterol Hepatol 2023; 15:665-687. [PMID: 36332814 PMCID: PMC9871441 DOI: 10.1016/j.jcmgh.2022.10.016] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 10/11/2022] [Accepted: 10/20/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND & AIMS Although appendectomy may reduce colorectal inflammation in patients with ulcerative colitis (UC), this surgical procedure has been suggested to be associated with an increased risk of colitis-associated cancer (CAC). Our aim was to explore the mechanism underlying the appendectomy-associated increased risk of CAC. METHODS Five-week-old male BALB/c mice underwent appendectomy, appendicitis induction, or sham laparotomy. They were then exposed to azoxymethane/dextran sodium sulfate (AOM/DSS) to induce CAC. Mice were killed 12 weeks later, and colons were taken for pathological analysis and immunohistochemistry (CD3 and CD8 staining). Human colonic tumors from 21 patients with UC who underwent surgical resection for CAC were immunophenotyped and stratified according to appendectomy status. RESULTS Whereas appendectomy significantly reduced colitis severity and increased CAC number, appendicitis induction without appendectomy led to opposite results. Intratumor CD3+ and CD8+ T-cell densities were lower after appendectomy and higher after appendicitis induction compared with the sham laparotomy group. Blocking lymphocyte trafficking to the colon with the anti-α4β7 integrin antibody or a sphingosine-1-phosphate receptor agonist suppressed the inducing effect of the appendectomy on tumors' number and on CD3+/CD8+ intratumoral density. CD8+ or CD3+ T cells isolated from inflammatory neo-appendix and intravenously injected into AOM/DSS-treated recipient mice increased CD3+/CD8+ T-cell tumor infiltration and decreased tumor number. In UC patients with a history of appendectomy, intratumor CD3+ and CD8+ T-cell densities were decreased compared with UC patients without history of appendectomy. CONCLUSIONS In UC, appendectomy could suppress a major site of T-cell priming, resulting in a less efficient CAC immunosurveillance.
Collapse
Affiliation(s)
- Maxime K Collard
- Assistance Publique Hôpitaux de Paris, Service de Chirurgie Colorectale, Hôpital Beaujon, Clichy, France; Université de Paris, Centre de Recherche sur l'Inflammation, INSERM, U1149, CNRS, ERL8252, "Gut Inflammation", Paris, France
| | - Julien Tourneur-Marsille
- Université de Paris, Centre de Recherche sur l'Inflammation, INSERM, U1149, CNRS, ERL8252, "Gut Inflammation", Paris, France
| | - Mathieu Uzzan
- Université de Paris, Centre de Recherche sur l'Inflammation, INSERM, U1149, CNRS, ERL8252, "Gut Inflammation", Paris, France; Assistance Publique Hôpitaux de Paris, Service de Gastroentérologie, Hôpital Beaujon, Clichy, France
| | - Miguel Albuquerque
- Assistance Publique Hôpitaux de Paris, Service d'Anatomopathologie, Hôpital Beaujon, Clichy, France
| | - Maryline Roy
- Université de Paris, Centre de Recherche sur l'Inflammation, INSERM, U1149, CNRS, ERL8252, "Gut Inflammation", Paris, France
| | - Anne Dumay
- Université de Paris, Centre de Recherche sur l'Inflammation, INSERM, U1149, CNRS, ERL8252, "Gut Inflammation", Paris, France
| | - Jean-Noël Freund
- Université de Strasbourg, Inserm, IRFAC / UMR-S1113, FHU ARRIMAGE, ITI InnoVec, FMTS, Strasbourg, France
| | - Jean-Pierre Hugot
- Université de Paris, Centre de Recherche sur l'Inflammation, INSERM, U1149, CNRS, ERL8252, "Gut Inflammation", Paris, France
| | - Nathalie Guedj
- Université de Paris, Centre de Recherche sur l'Inflammation, INSERM, U1149, CNRS, ERL8252, "Gut Inflammation", Paris, France; Assistance Publique Hôpitaux de Paris, Service d'Anatomopathologie, Hôpital Beaujon, Clichy, France
| | - Xavier Treton
- Université de Paris, Centre de Recherche sur l'Inflammation, INSERM, U1149, CNRS, ERL8252, "Gut Inflammation", Paris, France; Assistance Publique Hôpitaux de Paris, Service de Gastroentérologie, Hôpital Beaujon, Clichy, France
| | - Yves Panis
- Assistance Publique Hôpitaux de Paris, Service de Chirurgie Colorectale, Hôpital Beaujon, Clichy, France; Université de Paris, Centre de Recherche sur l'Inflammation, INSERM, U1149, CNRS, ERL8252, "Gut Inflammation", Paris, France
| | - Eric Ogier-Denis
- Université de Paris, Centre de Recherche sur l'Inflammation, INSERM, U1149, CNRS, ERL8252, "Gut Inflammation", Paris, France; INSERM, Université Rennes, CLCC Eugène Marquis, «Chemistry, Oncogenesis, Stress Signaling» UMR_S 1242, Rennes, France.
| |
Collapse
|
|
22
|
Pentosan Polysulfate-Associated Dysplasia in Patients with Inflammatory Bowel Disease: A Case Series. Am J Gastroenterol 2022; 118:905-908. [PMID: 36689730 DOI: 10.14309/ajg.0000000000002137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 11/21/2022] [Indexed: 01/25/2023]
Abstract
OBJECTIVES This study evaluates the potential association of pentosan polysulfate (PPS) with inflammatory bowel disease (IBD) or dysplasia. METHODS We searched electronic medical records to identify patients with IBD using PPS. RESULTS 10 of 30 identified patients (33.3%) had colonic dysplasia. Six of these (60%) underwent colectomy for endoscopically unresectable dysplasia. Three (10%) discontinued PPS, each with apparent benefit. CONCLUSIONS Patients with IBD at two institutions who had taken PPS had high rates of colonic dysplasia leading to surgery. Patients who stopped PPS showed improvement in their colitis. PPS may play a causal role in the development of colitis and dysplasia.
Collapse
|
|
23
|
Fabian O, Bajer L. Histopathological assessment of the microscopic activity in inflammatory bowel diseases: What are we looking for? World J Gastroenterol 2022; 28:5300-5312. [PMID: 36185628 PMCID: PMC9521520 DOI: 10.3748/wjg.v28.i36.5300] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 08/11/2022] [Accepted: 09/07/2022] [Indexed: 02/06/2023] Open
Abstract
Advances in diagnostics of inflammatory bowel diseases (IBD) and improved treatment strategies allowed the establishment of new therapeutic endpoints. Currently, it is desirable not only to cease clinical symptoms, but mainly to achieve endoscopic remission, a macroscopic normalization of the bowel mucosa. However, up to one-third of IBD patients in remission exhibit persisting microscopic activity of the disease. The evidence suggests a better predictive value of histology for the development of clinical complications such as clinical relapse, surgical intervention, need for therapy escalation, or development of colorectal cancer. The proper assessment of microscopic inflammatory activity thus became an important part of the overall histopathological evaluation of colonic biopsies and many histopathological scoring indices have been established. Nonetheless, a majority of them have not been validated and no scoring index became a part of the routine bioptic practice. This review summarizes a predictive value of microscopic disease activity assessment for the subsequent clinical course of IBD, describes the most commonly used scoring indices for Crohn's disease and ulcerative colitis, and comments on current limitations and unresolved issues.
Collapse
Affiliation(s)
- Ondrej Fabian
- Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine, Prague 14021, Czech Republic
- Department of Pathology and Molecular Medicine, 3rd Faculty of Medicine, Charles University and Thomayer Hospital, Prague 14059, Czech Republic
| | - Lukas Bajer
- Hepatogastroenterology Department, Institute for Clinical and Experimental Medicine, Prague 14021, Czech Republic
- Institute of Microbiology, Czech Academy of Sciences, Prague 14220, Czech Republic
| |
Collapse
|
|
24
|
Colorectal Cancer in Ulcerative Colitis: Mechanisms, Surveillance and Chemoprevention. Curr Oncol 2022; 29:6091-6114. [PMID: 36135048 PMCID: PMC9498229 DOI: 10.3390/curroncol29090479] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 08/14/2022] [Accepted: 08/18/2022] [Indexed: 11/17/2022] Open
Abstract
Patients with ulcerative colitis (UC) are at a two- to three-fold increased risk of developing colorectal cancer (CRC) than the general population based on population-based data. UC-CRC has generated a series of clinical problems, which are reflected in its worse prognosis and higher mortality than sporadic CRC. Chronic inflammation is a significant contributor to the development of UC-CRC, so comprehending the relationship between the proinflammatory factors and epithelial cells together with downstream signaling pathways is the core to elucidate the mechanisms involved in developing of CRC. Clinical studies have shown the importance of early prevention, detection and management of CRC in patients with UC, and colonoscopic surveillance at regular intervals with multiple biopsies is considered the most effective way. The use of endoscopy with targeted biopsies of visible lesions has been supported in most populations. In contrast, random biopsies in patients with high-risk characteristics have been suggested during surveillance. Some of the agents used to treat UC are chemopreventive, the effects of which will be examined in cancers in UC in a population-based setting. In this review, we outline the current state of potential risk factors and chemopreventive recommendations in UC-CRC, with a specific focus on the proinflammatory mechanisms in promoting CRC and evidence for personalized surveillance.
Collapse
|
|
25
|
Histological Scores in Patients with Inflammatory Bowel Diseases: The State of the Art. J Clin Med 2022; 11:jcm11040939. [PMID: 35207211 PMCID: PMC8880199 DOI: 10.3390/jcm11040939] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 02/07/2022] [Accepted: 02/08/2022] [Indexed: 02/07/2023] Open
Abstract
The histological assessment has been advocated as a detailed and accurate measure of disease activity in inflammatory bowel diseases (IBD). In ulcerative colitis (UC), histological activity has been demonstrated to be associated with higher rates of relapse, prolonged corticosteroid use and long-term complications, even when endoscopic remission is achieved. Therefore, histological healing may represent a potential treatment target. Several histological scores have been developed and are available today. The Robarts histopathology index (RHI) and the Nancy index (NI) are the only two recommended by the European Crohn’s and Colitis Organization (ECCO) for use in patients with UC. Conversely, in Crohn’s disease (CD), the discontinuous nature of lesions has limited standardized histological assessment. Most of the available histological scoring systems in CD are complex and not validated. The aim of this review is to comprehensively summarize the latest evidence regarding histological scoring systems in IBD. We guide the reader through understanding the importance of an accurate microscopic evaluation using validated scoring systems, highlighting the strengths and pitfalls of each score. The priorities of future research needs are also addressed.
Collapse
|
|
26
|
Damião AOMC, Queiroz NSF. Medical Therapy in Chronic Refractory Ulcerative Colitis: When Enough Is Enough. Clin Colon Rectal Surg 2022; 35:32-43. [PMID: 35069028 PMCID: PMC8763462 DOI: 10.1055/s-0041-1740036] [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: 01/19/2023]
Abstract
Despite significant improvements in the management of ulcerative colitis (UC) in parallel with the evolution of therapeutic targets and novel biologics and small molecules, a subset of medically refractory patients still requires colectomy. Recent population-based studies demonstrate a trend toward a decrease in the rates of surgery for UC patients in the biological era, although the potential of disease modification with these agents is still debated. As the concept of irreversible bowel damage is underexplored in UC, refractory patients can be exposed to multiple treatments losing optimal timing for surgery and further developing complications such as dysplasia/cancer, dysmotility, microcolon, and other functional abnormalities. This review aims to discuss the concept of disease progression in UC, explore the limitations of medical treatment in refractory UC patients, and propose the application of a three-step algorithm that allows timely indication for surgery in clinical practice.
Collapse
Affiliation(s)
| | - Natália Sousa Freitas Queiroz
- Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil,Address for correspondence Natália Sousa Freitas Queiroz, MD, PhD Department of Gastroenterology, University of São Paulo School of MedicineSão Paulo 05403-000Brazil
| |
Collapse
|
|
27
|
He DG, Chen XJ, Huang JN, Chen JG, Lv MY, Huang TZ, Lan P, He XS. Increased risk of colorectal neoplasia in inflammatory bowel disease patients with post-inflammatory polyps: A systematic review and meta-analysis. World J Gastrointest Oncol 2022; 14:348-361. [PMID: 35116121 PMCID: PMC8790428 DOI: 10.4251/wjgo.v14.i1.348] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 09/08/2021] [Accepted: 11/24/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) patients with post-inflammatory polyps (PIPs) may carry an increased risk of colorectal neoplasia (CRN) including dysplasia and cancer. Current guidelines recommend active colonoscopy follow-up for these patients. However, the evidence for guidelines is still poor. In addition, some recent high-quality reports present a different view, which challenges the current guidelines. We hypothesize that IBD patients with PIPs are at increased risk of CRN. AIM To evaluate the risk of CRN in IBD patients with and without PIPs. METHODS A systematic search of PubMed, Embase, Cochrane Library, and Web of Science was performed to identify studies that compared the risk of CRN in IBD patients with and without PIPs. In addition, we screened the reference lists and citation indices of the included studies. Quality assessment was performed using the Newcastle-Ottawa Scale. Pooled odds ratio (OR) was calculated using the random-effects model to explore the final pooled effect size of the included studies and determine whether PIPs increase the risk of CRN. Sensitivity analysis, subgroup analysis, and assessment of publication bias were performed to examine the sources of heterogeneity. RESULTS Twelve studies with 5819 IBD patients, including 1281 (22.01%) with PIPs, were considered eligible for this meta-analysis. We found that IBD patients with PIPs were at an increased risk of CRN as compared to those without PIPs [OR 2.01; 95% confidence interval (CI): 1.43-2.83]. The results were similar when colorectal cancer was used as the study endpoint (OR 2.57; 95%CI: 1.69-3.91). Furthermore, the risk of CRN was still increased (OR 1.80; 95%CI: 1.12-2.91) when restricted to ulcerative colitis patients. Heterogeneity was high among the included studies (I² = 75%). Subgroup analysis revealed that the high heterogeneity was due to the study design. Sensitivity analysis showed that the main statistical outcomes did not essentially change after excluding any one of the included studies. No significant publication bias was found in the funnel plots. CONCLUSION IBD patients with PIPs have an increased risk of CRN as compared with those without PIPs, which support the current guidelines. However, a high-quality randomized controlled trial is warranted.
Collapse
Affiliation(s)
- De-Gao He
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou 510655, Guangdong Province, China
| | - Xi-Jie Chen
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou 510655, Guangdong Province, China
| | - Juan-Ni Huang
- Department of Geriatrics, the first Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, Guangdong Province, China
| | - Jun-Guo Chen
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou 510655, Guangdong Province, China
| | - Min-Yi Lv
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou 510655, Guangdong Province, China
| | - Tian-Ze Huang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou 510655, Guangdong Province, China
| | - Ping Lan
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou 510655, Guangdong Province, China
| | - Xiao-Sheng He
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou 510655, Guangdong Province, China
| |
Collapse
|
|
28
|
Pai RK, Lauwers GY, Pai RK. Measuring Histologic Activity in Inflammatory Bowel Disease: Why and How. Adv Anat Pathol 2022; 29:37-47. [PMID: 34879037 DOI: 10.1097/pap.0000000000000326] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Histology is used to confirm the diagnosis of inflammatory bowel disease, exclude superimposed infections, and to evaluate for dysplasia. Histology has rarely been used to measure disease activity and guide therapy despite evidence that histologic measurements have value in predicting important clinical outcomes. More recently, there have been numerous studies supporting a role for histologic disease activity measurements in predicting a variety of outcomes including relapse, hospitalizations, steroid use, and dysplasia. The histologic assessment was superior to endoscopic measurements in many of these studies. This review will summarize the recent literature regarding histologic disease activity measurements in ulcerative colitis and Crohn disease. A detailed description of histologic scoring systems will also be provided to provide pathologists with the necessary tools to accurately measure disease activity.
Collapse
Affiliation(s)
- Reetesh K Pai
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA
| | | | - Rish K Pai
- Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ
| |
Collapse
|
|
29
|
Wetwittayakhlang P, Lontai L, Gonczi L, Golovics PA, Hahn GD, Bessissow T, Lakatos PL. Treatment Targets in Ulcerative Colitis: Is It Time for All In, including Histology? J Clin Med 2021; 10:5551. [PMID: 34884252 PMCID: PMC8658443 DOI: 10.3390/jcm10235551] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 11/23/2021] [Accepted: 11/24/2021] [Indexed: 02/06/2023] Open
Abstract
The main therapeutic goal of ulcerative colitis (UC) is to induce and maintain remission to prevent long-term disease progression. Treat-to-target strategies, first introduced by the STRIDE consensus and updated in 2021, have shifted focus from symptomatic control toward more stringent objective endpoints. Today, patient monitoring should be based on a combination of biomarkers and clinical scores, while patient-reported outcomes could be used as short-term targets in monitoring disease activity and therapeutic response. In addition, endoscopic healing was the preferred long-term goal in UC. A Mayo endoscopic score (MES) ≤ 1 can be recommended as a minimum target. However, recent evidence suggests that more stringent endoscopic goals (MES of 0) are associated with superior outcomes. Recently, emerging data support that histological remission (HR) is a superior prognostic factor to endoscopic healing in predicting long-term remission. Despite not yet being recommended as a target, HR may become an important potential therapeutic goal in UC. However, it remains questionable if histological healing should be used as a routine assessment in addition to clinical, biomarker, and endoscopic targets in all patients. Therefore, in this review, our aim was to discuss the current evidence for the different treatment targets and their value in everyday clinical practice.
Collapse
Affiliation(s)
- Panu Wetwittayakhlang
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (P.A.G.); (G.D.H.); (T.B.)
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand
| | - Livia Lontai
- First Department of Medicine, Semmelweis University, H-1083 Budapest, Hungary; (L.L.); (L.G.)
| | - Lorant Gonczi
- First Department of Medicine, Semmelweis University, H-1083 Budapest, Hungary; (L.L.); (L.G.)
| | - Petra A. Golovics
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (P.A.G.); (G.D.H.); (T.B.)
- Department of Gastroenterology, Hungarian Defence Forces, Medical Centre, H-1062 Budapest, Hungary
| | - Gustavo Drügg Hahn
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (P.A.G.); (G.D.H.); (T.B.)
- Graduate Course Sciences in Gastroenterology and Hepatology, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-002, Brazil
| | - Talat Bessissow
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (P.A.G.); (G.D.H.); (T.B.)
| | - Peter L. Lakatos
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (P.A.G.); (G.D.H.); (T.B.)
- First Department of Medicine, Semmelweis University, H-1083 Budapest, Hungary; (L.L.); (L.G.)
| |
Collapse
|
|
30
|
Probiotics in Intestinal Mucosal Healing: A New Therapy or an Old Friend? Pharmaceuticals (Basel) 2021; 14:ph14111181. [PMID: 34832962 PMCID: PMC8622522 DOI: 10.3390/ph14111181] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/08/2021] [Accepted: 11/18/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel disease (IBD), Crohn’s disease, and ulcerative colitis are characterized by chronic and relapsing inflammation, while their pathogenesis remains mostly unelucidated. Gut commensal microbiota seem to be one of the various implicated factors, as several studies have shown a significant decrease in the microbiome diversity of patients with IBD. Although the question of whether microbiota dysbiosis is a causal factor or the result of chronic inflammation remains unanswered, one fact is clear; active inflammation in IBD results in the disruption of the mucus layer structure, barrier function, and also, colonization sites. Recently, many studies on IBD have been focusing on the interplay between mucosal and luminal microbiota, underlining their possible beneficial effect on mucosal healing. Regarding this notion, it has now been shown that specific probiotic strains, when administrated, lead to significantly decreased inflammation, amelioration of colitis, and improved mucosal healing. Probiotics are live microorganisms exerting beneficial effects on the host’s health when administered in adequate quantity. The aim of this review was to present and discuss the current findings on the role of gut microbiota and their metabolites in intestinal wound healing and the effects of probiotics on intestinal mucosal wound closure.
Collapse
|
|
31
|
Fumery M, Chatelain D. Histological Scores in Inflammatory Bowel Disease: A New Kid in the Block. J Crohns Colitis 2021; 15:1603-1604. [PMID: 34042152 DOI: 10.1093/ecco-jcc/jjab083] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Affiliation(s)
- Mathurin Fumery
- Department of Gastroenterology, Amiens University Medical Center and Jules Verne University of Picardie, Amiens, France
| | - Denis Chatelain
- Department of Pathology Unit, Amiens University Medical Center and Jules Verne University of Picardie, Amiens, France
| |
Collapse
|
|
32
|
Novel Bioenhanced Curcumin With Mesalamine for Induction of Clinical and Endoscopic Remission in Mild-to-Moderate Ulcerative Colitis: A Randomized Double-Blind Placebo-controlled Pilot Study. J Clin Gastroenterol 2021; 55:702-708. [PMID: 32889959 DOI: 10.1097/mcg.0000000000001416] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 07/29/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS The aim of this study was to assess the efficacy and safety of a novel, hydrophilic, bioenhanced curcumin (BEC) as add-on therapy in inducing clinical and endoscopic remission in mild to moderately active ulcerative colitis (UC). DESIGN Mild to moderately active UC patients (partial Mayo score 2 to 6 with endoscopic Mayo score >1) on standard dose of mesalamine were randomized to either 50 mg twice daily BEC or an identical placebo. Clinical response (≥2 reduction of partial Mayo score), clinical remission (partial Mayo score ≤1), and endoscopic remission (endoscopic Mayo score of ≤1) were evaluated at 6 weeks and 3 months. Responders were followed-up at 6 and 12 months for assessing maintenance of remission. RESULTS Sixty-nine patients were randomly assigned to BEC (n=34) and placebo (n=35). At 6 weeks, clinical and endoscopic remission occurred in 44.1% (15/34) and 35.3% (14/34) patients, respectively, compared with none in the placebo group (P<0.01). Clinical response was also significantly higher in the BEC group (18/34, 52.9%) compared with placebo (5/35, 14.3%) (P=0.001). The clinical remission, clinical response, and endoscopic remission rates at 3 months were 55.9% (19/34), 58.8% (20/34), 44% (16/34) and 5.7% (2/35), 28.6% (10/35), 5.7% (2/35) in BEC and placebo groups, respectively. At 6 and 12 months, 95% (18/19) and 84% (16/19) of the responders to BEC maintained clinical remission. None of the responders to placebo maintained clinical remission at 6 months. BEC appeared safe with no significant side effects. CONCLUSION A low-dose BEC as add-on therapy was superior to placebo in inducing sustained clinical and endoscopic remission in patients with mild-to-moderately active UC on maximal dose of mesalamine (ClinicalTrials.gov: NCT02683733).
Collapse
|
|
33
|
Gupta A, Yu A, Peyrin-Biroulet L, Ananthakrishnan AN. Treat to Target: The Role of Histologic Healing in Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2021; 19:1800-1813.e4. [PMID: 33010406 DOI: 10.1016/j.cgh.2020.09.046] [Citation(s) in RCA: 88] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 09/17/2020] [Accepted: 09/20/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Endoscopic remission is a recognized therapeutic endpoint in inflammatory bowel disease (IBD; Crohn's disease (CD), ulcerative colitis (UC)). The impact of persistent histologic activity on long-term outcomes is less clear and limited by small studies. METHODS We performed a systematic search of PubMed and Embase to identify eligible studies examining the association between histologic activity and relapse in patients with CD or UC in endoscopic remission. Studies were pooled together using random effects meta-analysis per the DerSimonian and Laird inverse variance method. The impact of different histologic scales, cut-offs, and individual features were examined. FINDINGS Our meta-analysis included 28 studies contributing 2,806 patients (2677 UC; 129 CD). In UC, histologically active disease was associated with an overall increased risk of relapse (OR, 2.41; 95% CI, 1.91-3.04), with a similar effect noted in the subgroup with endoscopic Mayo endoscopic score of 0 vs 0 or 1. More rigorous Geboes cut-offs demonstrated numerically stronger impact on relapse rates-Geboes <3.1 (OR, 2.40; 95% CI, 1.57-3.65), Geboes <2.1 (OR, 3.91; 95% CI, 2.21-6.91) and Geboes 0 (OR, 7.40; 95% CI, 2.00-18.27). Among individual histologic features, basal plasmacytosis (OR, 1.94), neutrophilic infiltrations (OR, 2.30), mucin depletion (OR, 2.05), and crypt architectural irregularities (OR, 2.22) predicted relapse. There was no association between histologic activity and relapse in CD. CONCLUSIONS In patients with UC in endoscopic remission, persistent histologic activity is associated with higher rates of relapse. Greater degree of normalization may have a stronger impact.
Collapse
Affiliation(s)
- Akshita Gupta
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Amy Yu
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Vandoeuvre-les-Nancy, France; French Institute of Health and Medical Research U1256 NGERE, University of Lorraine, Vandoeuvre-les-Nancy, France
| | - Ashwin N Ananthakrishnan
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Department of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
| |
Collapse
|
|
34
|
Fukumoto Y, Kobayashi Y, Takemura S, Maeda K, Nakamura F, Inatomi O, Andoh A, Ban H. A case of appendix adenocarcinoma associated with ulcerative colitis. Clin Case Rep 2021; 9:e04768. [PMID: 34484784 PMCID: PMC8405520 DOI: 10.1002/ccr3.4768] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Revised: 08/12/2021] [Accepted: 08/13/2021] [Indexed: 11/25/2022] Open
Abstract
Ulcerative colitis (UC) is a chronic relapsing inflammatory disorder of the colon. Patients with UC have an increased risk of developing colorectal cancer. However, appendix adenocarcinoma associated with UC is extremely rare.
Collapse
Affiliation(s)
- Yohsuke Fukumoto
- Division of GastroenterologyKusatsu General HospitalKusatsuJapan
| | - Yuh Kobayashi
- Division of GastroenterologyKusatsu General HospitalKusatsuJapan
| | | | - Kiyosumi Maeda
- Division of RadiologyKusatsu General HospitalKusatsuJapan
| | | | - Osamu Inatomi
- Department of MedicineShiga University of Medical ScienceKusatsuJapan
| | - Akira Andoh
- Department of MedicineShiga University of Medical ScienceKusatsuJapan
| | - Hiromitsu Ban
- Division of GastroenterologyKusatsu General HospitalKusatsuJapan
| |
Collapse
|
|
35
|
Liu S, Eisenstein S. State-of-the-art surgery for ulcerative colitis. Langenbecks Arch Surg 2021; 406:1751-1761. [PMID: 34453611 PMCID: PMC8481179 DOI: 10.1007/s00423-021-02295-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 08/04/2021] [Indexed: 12/11/2022]
Abstract
Ulcerative colitis (UC) is an autoimmune-mediated colitis which can present in varying degrees of severity and increases the individual’s risk of developing colon cancer. While first-line treatment for UC is medical management, surgical treatment may be necessary in up to 25–30% of patients. With an increasing armamentarium of biologic therapies, patients are presenting for surgery much later in their course, and careful understanding of the complex interplay of the disease, its management, and the patient’s overall health is necessary when considering he appropriate way in which to address their disease surgically. Surgery is generally a total proctocolectomy either with pelvic pouch reconstruction or permanent ileostomy; however, this may need to be spread across multiple procedures given the complexity of the surgery weighed against the overall state of the patient’s health. Minimally invasive surgery, employing either laparoscopic, robotic, or transanal laparoscopic approaches, is currently the preferred approach in the elective setting. There is also some emerging evidence that appendectomy may delay the progression of UC in some individuals. Those who treat these patients surgically must also be familiar with the numerous potential pitfalls of surgical intervention and have plans in place for managing problems such as pouchitis, cuffitis, and anastomotic complications.
Collapse
Affiliation(s)
- Shanglei Liu
- Department of Surgery, UC San Diego Health System, 3855 Health Sciences Dr. #0987, La Jolla, CA, 92093, USA
| | - Samuel Eisenstein
- Department of Surgery, UC San Diego Health System, 3855 Health Sciences Dr. #0987, La Jolla, CA, 92093, USA.
| |
Collapse
|
|
36
|
Wang T, Zhang L, Wang P, Liu Y, Wang G, Shan Y, Yi Y, Zhou Y, Liu B, Wang X, Lü X. Lactobacillus coryniformis MXJ32 administration ameliorates azoxymethane/dextran sulfate sodium-induced colitis-associated colorectal cancer via reshaping intestinal microenvironment and alleviating inflammatory response. Eur J Nutr 2021; 61:85-99. [PMID: 34185157 DOI: 10.1007/s00394-021-02627-8] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 06/24/2021] [Indexed: 12/24/2022]
Abstract
PURPOSE Gut microbiota has been reported to contribute to either prevent or promote colorectal cancer (CRC), and treatment with probiotics might be a promising intervention method. The present study aimed to evaluate the potential anti-CRC effects of Lactobacillus coryniformis MXJ32 on a colitis-associated (CA)-CRC mouse model. METHODS The CA-CRC mouse model was induced by a single intraperitoneal injection of 10 mg/kg azoxymethane and followed by three 7-day cycles of 2% dextran sulfate sodium in drinking water with a 14-day recovery period. Mice were supplemented with L. coryniformis MXJ32 by oral gavage (1 × 109 CFU/day/mouse). The CA-CRC attenuating effects of this probiotic were assessed via intestinal barrier integrity, inflammation, and gut microenvironment. RESULTS Treatment with L. coryniformis MXJ32 could significantly inhibit the total number of tumors and the average tumor diameter. This probiotic administration prevented the damage of intestinal barrier function by enhancing the expression of tight junction proteins (Occludin, Claudin-1, and ZO-1) and recovering the loss of goblet cells. Moreover, L. coryniformis MXJ32 alleviated intestinal inflammation via down-regulating the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-γ, and IL-17a) and chemokines (Cxcl1, Cxcl2, Cxcl3, Cxcl5, and Ccl7). In addition, L. coryniformis MXJ32 supplementation increased the abundance of some beneficial bacteria (such as SCFAs-producing bacteria, Lactobacillus, Bifidobacterium, Akkermansia, and Faecalibaculum) and decreased the abundance of some harmful bacteria (such as pro-inflammatory bacteria, Desulfovibrio and Helicobacter), which in turn attenuated the overexpression of inflammation. CONCLUSION Lactobacillus coryniformis MXJ32 could effectively ameliorate CA-CRC via regulating intestinal microenvironment, alleviating inflammation, and intestinal barrier damage, which further suggested that L. coryniformis MXJ32 could be considered as a functional food ingredient for the alleviation of CA-CRC.
Collapse
Affiliation(s)
- Tao Wang
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China
| | - Leshan Zhang
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China
| | - Panpan Wang
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China
| | - Yilin Liu
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China
| | - Gangtu Wang
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China
| | - Yuanyuan Shan
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China
| | - Yanglei Yi
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China
| | - Yuan Zhou
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China
| | - Bianfang Liu
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China.
| | - Xin Wang
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China.
| | - Xin Lü
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China.
| |
Collapse
|
|
37
|
Yalchin M, Baker AM, Graham TA, Hart A. Predicting Colorectal Cancer Occurrence in IBD. Cancers (Basel) 2021; 13:2908. [PMID: 34200768 PMCID: PMC8230430 DOI: 10.3390/cancers13122908] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 05/27/2021] [Accepted: 06/01/2021] [Indexed: 12/13/2022] Open
Abstract
Patients with colonic inflammatory bowel disease (IBD) are at an increased risk of developing colorectal cancer (CRC), and are therefore enrolled into a surveillance programme aimed at detecting dysplasia or early cancer. Current surveillance programmes are guided by clinical, endoscopic or histological predictors of colitis-associated CRC (CA-CRC). We have seen great progress in our understanding of these predictors of disease progression, and advances in endoscopic technique and management, along with improved medical care, has been mirrored by the falling incidence of CA-CRC over the last 50 years. However, more could be done to improve our molecular understanding of CA-CRC progression and enable better risk stratification for patients with IBD. This review summarises the known risk factors associated with CA-CRC and explores the molecular landscape that has the potential to complement and optimise the existing IBD surveillance programme.
Collapse
Affiliation(s)
- Mehmet Yalchin
- Inflammatory Bowel Disease Department, St. Mark’s Hospital, Watford R.d., Harrow HA1 3UJ, UK
- Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse S.q., London EC1M 6BQ, UK; (A.-M.B.); (T.A.G.)
| | - Ann-Marie Baker
- Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse S.q., London EC1M 6BQ, UK; (A.-M.B.); (T.A.G.)
| | - Trevor A. Graham
- Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse S.q., London EC1M 6BQ, UK; (A.-M.B.); (T.A.G.)
| | - Ailsa Hart
- Inflammatory Bowel Disease Department, St. Mark’s Hospital, Watford R.d., Harrow HA1 3UJ, UK
| |
Collapse
|
|
38
|
Sakuraba A, Nemoto N, Hibi N, Ozaki R, Tokunaga S, Kikuchi O, Minowa S, Mitsui T, Miura M, Saito D, Hayashida M, Miyoshi J, Matsuura M, Yoneyama M, Ohnishi H, Hisamatsu T. Extent of disease affects the usefulness of fecal biomarkers in ulcerative colitis. BMC Gastroenterol 2021; 21:197. [PMID: 33933033 PMCID: PMC8088576 DOI: 10.1186/s12876-021-01788-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Accepted: 04/23/2021] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Fecal biomarkers are considered to be useful surrogate markers for endoscopic activity. Given the mechanisms of fecal biomarkers, we hypothesized that the extent of ulcerative colitis (UC; pancolitis, left-sided colitis, and proctitis) could affect the usefulness of fecal biomarkers for assessing endoscopic and clinical disease activity; however, few studies have evaluated the utility of fecal biomarkers in the disease extent of UC. METHODS Fecal calprotectin, a fecal immunochemical test for hemoglobin, and fecal lactoferrin were used as fecal biomarkers. UC patients, who underwent colonoscopy within 30 days of the fecal biomarker test, participated in this observational study. Clinical and endoscopic disease activity was assessed using the Lichtiger Index and Mayo endoscopic subscore (MES), respectively. RESULTS A total of 162 colonoscopies were performed on 133 UC patients. A correlation analysis between each biomarker and the MES for each disease-extent subgroup showed a decreased correlation in the proctitis compared with the other groups. With the exception of proctitis, it was possible to distinguish between MES 0 and MES ≥ 1 with high area-under-the-curve values for fecal calprotectin and fecal lactoferrin. The fecal immunochemical test for hemoglobin was superior at discriminating MES 0 for proctitis. CONCLUSIONS For the practical application of fecal biomarkers for UC patients, it is necessary to consider disease extent before use. In particular, patients with proctitis exhibit a low correlation between stool biomarkers and endoscopic findings. The usefulness of these biomarkers for endoscopic remission is reduced, except for the fecal immunochemical test for hemoglobin.
Collapse
Affiliation(s)
- Akihito Sakuraba
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
| | - Nobuki Nemoto
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
| | - Noritaka Hibi
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
| | - Ryo Ozaki
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
| | - Sotaro Tokunaga
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
| | - Oki Kikuchi
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
| | - Shintaro Minowa
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
| | - Tatsuya Mitsui
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
| | - Miki Miura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
| | - Daisuke Saito
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
| | - Mari Hayashida
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
| | - Jun Miyoshi
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
| | - Minoru Matsuura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
| | - Masayoshi Yoneyama
- Department of Clinical Laboratory, Kyorin University Hospital, Tokyo, Japan
| | - Hiroaki Ohnishi
- Department of Laboratory Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan.
| |
Collapse
|
|
39
|
Recommendations of the Spanish Working Group on Crohn's disease and Ulcerative Colitis (Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa - GETECCU) on dysplasia screening in inflammatory bowel disease patients. GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 44:435-447. [PMID: 33592179 DOI: 10.1016/j.gastrohep.2020.12.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 12/21/2020] [Indexed: 12/12/2022]
Abstract
Colonic inflammatory bowel diseases have a higher risk of developing colorectal cancer compared to the general population, which is why they require endoscopic screening techniques with specific follow-up intervals based on the different risk factors described on the literature. This position paper analyzes the current scientific evidence for the different endoscopic techniques available today, how their implementation should be carried out in endoscopic units and describes in detail how their implementation should be carried out, in which patients and with what interval, and finally, what should be the response to finding dysplasia, proposing a specific follow-up algorithm.
Collapse
|
|
40
|
Liu P, Wang Y, Yang G, Zhang Q, Meng L, Xin Y, Jiang X. The role of short-chain fatty acids in intestinal barrier function, inflammation, oxidative stress, and colonic carcinogenesis. Pharmacol Res 2021; 165:105420. [PMID: 33434620 DOI: 10.1016/j.phrs.2021.105420] [Citation(s) in RCA: 388] [Impact Index Per Article: 97.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 12/25/2020] [Accepted: 01/04/2021] [Indexed: 12/12/2022]
Abstract
Short-chain fatty acids (SCFAs), mainly including acetate, propionate, and butyrate, are metabolites produced during the bacterial fermentation of dietary fiber in the intestinal tract. They are believed to be essential factors affecting host health. Most in vitro and ex vivo studies have shown that SCFAs affect the regulation of inflammation, carcinogenesis, intestinal barrier function, and oxidative stress, but convincing evidence in humans is still lacking. Two major SCFA signaling mechanisms have been identified: promotion of histone acetylation and activation of G-protein-coupled receptors. In this review, we introduce the production and metabolic characteristics of SCFAs, summarize the potential effects of SCFAs on the four aspects mentioned above and the possible mechanisms. SCFAs have been reported to exert a wide spectrum of positive effects and have a high potential for therapeutic use in human-related diseases.
Collapse
Affiliation(s)
- Pinyi Liu
- Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China; Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China; Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, China.
| | - Yanbing Wang
- Department of Orthopedic, The Second Hospital of Jilin University, Changchun, 130041, China.
| | - Ge Yang
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China.
| | - Qihe Zhang
- Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China; Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China.
| | - Lingbin Meng
- Department of Hematology and Medical Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA.
| | - Ying Xin
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China.
| | - Xin Jiang
- Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China; Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, China.
| |
Collapse
|
|
41
|
Zeng J, Meng ZM, Huang XL, Gan HT. Effects of 5-aminosalicylates or thiopurines on the progression of low-grade dysplasia in patients with inflammatory bowel disease: a systematic review and meta-analysis. Int J Colorectal Dis 2021; 36:11-18. [PMID: 32870327 DOI: 10.1007/s00384-020-03735-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/26/2020] [Indexed: 02/05/2023]
Abstract
PURPOSE Although 5-aminosalicylates and thiopurines may have an antineoplastic effect on colorectal neoplasia in patients with inflammatory bowel disease (IBD), their impact on the progression of low-grade dysplasia (LGD) in IBD is uncertain. Therefore, we performed a systematic review and meta-analysis to evaluate whether 5-aminosalicylates or thiopurines can protect against the progression of LGD in patients with IBD. METHODS Systematic searches of PubMed, EMBASE, Cochrane Library databases, and major conference proceedings were conducted to identify all eligible studies through March 2020. Data were pooled using a random effects model. Study quality was assessed using the Newcastle-Ottawa Scale. RESULTS Five studies comprising 776 IBD patients with LGD were included. Overall, 5-aminosalicylates (Hazard ratio (HR) = 0.91, 95% confidence interval (CI) 0.55-1.51) and thiopurines (HR = 0.64, 95% CI 0.23-1.79) did not significantly reduce the risk of advanced colorectal neoplasia (high-grade dysplasia/cancer) in IBD patients with LGD. Moreover, the effects of 5-aminosalicylates or thiopurines on risk of advanced colorectal neoplasia in IBD patients with LGD were not significant by different primary sclerosing cholangitis status, study quality, sample size, and IBD type. CONCLUSIONS In this study, we did not find a significant protective effect of 5-aminosalicylates or thiopurines on the progression of LGD in patients with IBD.
Collapse
Affiliation(s)
- Jian Zeng
- Division of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Zhang-Min Meng
- The Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Xiao-Li Huang
- The Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
| | - Hua-Tian Gan
- Division of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.
- The Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
- The Center of Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China.
| |
Collapse
|
|
42
|
Alkhatry M, Al-Rifai A, Annese V, Georgopoulos F, Jazzar AN, Khassouan AM, Koutoubi Z, Nathwani R, Taha MS, Limdi JK. First United Arab Emirates consensus on diagnosis and management of inflammatory bowel diseases: A 2020 Delphi consensus. World J Gastroenterol 2020; 26:6710-6769. [PMID: 33268959 PMCID: PMC7684461 DOI: 10.3748/wjg.v26.i43.6710] [Citation(s) in RCA: 10] [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: 04/16/2020] [Revised: 07/15/2020] [Accepted: 10/12/2020] [Indexed: 02/06/2023] Open
Abstract
Ulcerative colitis and Crohn's disease are the main entities of inflammatory bowel disease characterized by chronic remittent inflammation of the gastrointestinal tract. The incidence and prevalence are on the rise worldwide, and the heterogeneity between patients and within individuals over time is striking. The progressive advance in our understanding of the etiopathogenesis coupled with an unprecedented increase in therapeutic options have changed the management towards evidence-based interventions by clinicians with patients. This guideline was stimulated and supported by the Emirates Gastroenterology and Hepatology Society following a systematic review and a Delphi consensus process that provided evidence- and expert opinion-based recommendations. Comprehensive up-to-date guidance is provided regarding diagnosis, evaluation of disease severity, appropriate and timely use of different investigations, choice of appropriate therapy for induction and remission phase according to disease severity, and management of main complications.
Collapse
Affiliation(s)
- Maryam Alkhatry
- Gastroenterology and Endoscopy Department, Ibrahim Bin Hamad Obaid Allah Hospital, Ministry of Health and Prevention, Ras Al Khaiman, United Arab Emirates
| | - Ahmad Al-Rifai
- Department of Gastroenterology, Sheikh Shakbout Medical City, Abu Dhabi, United Arab Emirates
| | - Vito Annese
- Department of Gastroenterology, Valiant Clinic, Dubai, United Arab Emirates
- Department of Gastroenterology and Endoscopy, American Hospital, Dubai, United Arab Emirates
| | | | - Ahmad N Jazzar
- Gastroenterology Division, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Ahmed M Khassouan
- Digestive Disease Unit, Rashid Hospital, Dubai, United Arab Emirates
| | - Zaher Koutoubi
- Digestive Disease Institute, Cleveland Clinic, Abu Dhabi, United Arab Emirates
| | - Rahul Nathwani
- Department of Gastroenterology, Mediclinic City Hospital, Dubai, United Arab Emirates
- Department of Gastroenterology, Mohammed Bin Rashid University, Dubai, United Arab Emirates
| | - Mazen S Taha
- Gastroenterology and Hepatology, Tawam Hospital, Al Ain, United Arab Emirates
| | - Jimmy K Limdi
- Department of Gastroenterology, The Pennine Acute Hospitals NHS Trust, Manchester Academic Health Sciences, University of Manchester, Manchester M8 5RB, United Kingdom
| |
Collapse
|
|
43
|
Magro F, Doherty G, Peyrin-Biroulet L, Svrcek M, Borralho P, Walsh A, Carneiro F, Rosini F, de Hertogh G, Biedermann L, Pouillon L, Scharl M, Tripathi M, Danese S, Villanacci V, Feakins R. ECCO Position Paper: Harmonization of the Approach to Ulcerative Colitis Histopathology. J Crohns Colitis 2020; 14:1503-1511. [PMID: 32504534 DOI: 10.1093/ecco-jcc/jjaa110] [Citation(s) in RCA: 122] [Impact Index Per Article: 24.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Currently, the main targets of drug therapy for ulcerative colitis [UC] are endoscopic and clinical remission. However, there is active discussion about the additional advantages of including histological remission as a target. Accumulating evidence indicates that microscopic activity persists in endoscopically quiescent UC, that histological changes may lag behind clinical remission after treatment, and that absence of histological activity predicts lower rates of relapse, hospitalization, surgery and subsequent neoplasia. Obtaining useful information from mucosal biopsies in this setting depends on accurate and consistent evaluation of histological features. However, there is no standardization of biopsy procedures, histological sample processing technique or histological scoring systems, and there is no agreement on the definitions of histological remission, response or activity. Accordingly, a consensus expert panel convened by the European Crohn's and Colitis Organisation [ECCO] reviewed the literature and agreed a number of position statements regarding harmonization of UC histopathology. The objective was to provide evidence-based guidance for the standardization and harmonization of procedures, definitions and scoring systems for histology in UC, and to reach expert consensus where possible. We propose the absence of intraepithelial neutrophils, erosion and ulceration as a minimum requirement for the definition of histological remission. For randomized control trials we recommend the use of the Robarts histopathology index [RHI] or the Nancy index [NI]. For observational studies or in clinical practice we recommend the use of the NI. To predict the risk of future neoplasia in UC, cumulative histological scores over time are more useful than single scores.
Collapse
Affiliation(s)
- Fernando Magro
- Department of Gastroenterology, Centro Hospitalar Universitário São João, Porto, Portugal.,Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.,Department of Clinical Pharmacology, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Glen Doherty
- School of Medicine & Medical Science, University College Dublin, Dublin, Ireland
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Vandoeuvre-Les-Nancy, France.,Inserm U1256 NGERE, Lorraine University, Vandoeuvre-Les-Nancy, France
| | - Magali Svrcek
- Sorbonne Université, AP-HP, Hôpital Saint-Antoine, Department of Pathology, 184 rue du Faubourg Saint-Antoine, Paris, France
| | - Paula Borralho
- Department of Pathology, Hospital Cuf Descobertas, Lisboa and Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Alissa Walsh
- Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK
| | - Fatima Carneiro
- Department of Pathology, Faculty of Medicine of the University of Porto (FMUP) & Centro Hospitalar Universitário de São João (CHUSJ), Porto, Portugal.,Instituto de Investigação e Inovação em Saúde (i3S) & Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), Porto, Portugal
| | - Francesca Rosini
- Department of Cellular Pathology, North West London Pathology, Imperial College Healthcare NHS Trust, London, UK
| | - Gert de Hertogh
- Pathology Lab, UZ Gasthuisberg and KULeuven, Leuven, Belgium
| | - Luc Biedermann
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Lieven Pouillon
- Imelda GI Clinical Research Center, Imeldaziekenhuis Bonheiden, Bonheiden, Belgium
| | - Michael Scharl
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Monika Tripathi
- Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,IBD center, Department of Gastroenterology, Humanitas Clinical and Research Center, IRCCS, Milan, Italy
| | - Vincenzo Villanacci
- Department of Histopathology, Spedali Civili and University of Brescia, Brescia, Italy
| | - Roger Feakins
- Department of Cellular Pathology, Royal Free Hospital, London, UK
| |
Collapse
|
|
44
|
Vitello A, Shahini E, Macaluso FS, Morreale GC, Sinagra E, Pallio S, Maida M. Endoscopic surveillance of colorectal cancer in inflammatory bowel diseases: a review of the literature. Expert Rev Anticancer Ther 2020; 20:851-863. [PMID: 32811225 DOI: 10.1080/14737140.2020.1813030] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 08/18/2020] [Indexed: 02/08/2023]
Abstract
INTRODUCTION The risk of colorectal cancer (CRC) in patients with inflammatory bowel diseases (IBD) is higher compared to the general population and it is related to the type, severity, duration, and extension of the disease. AREAS COVERED This review aims to highlight current evidence from the literature supporting the role of endoscopic surveillance of CRC in patients with IBD. EXPERT OPINION Even in the absence of randomized controlled trials (RCTs), evidence from the literature supports the effectiveness of endoscopic surveillance in reducing IBD-related CRC incidence and mortality. As a consequence, current guidelines recommend colonoscopy 8-10 years after disease or symptom onset in all patients with ulcerative colitis (UC) and Crohn's disease (CD) involving at least one-third of the colon and agree on the necessity of annual surveillance in high-risk patients. Nevertheless, an overall agreement on the optimal intervals for surveillance of low-intermediate risk patients is absent and 2-5 year intervals have been proposed. In the near future, further studies are needed to assess the most effective intervals and tailor the surveillance based on the personal risk profile. Additionally, further efforts should be made to evaluate the role of noninvasive tests as primary screening, thus avoiding unnecessary colonoscopies.
Collapse
Affiliation(s)
- Alessandro Vitello
- Gastroenterology and Endoscopy Unit, S. Elia-Raimondi Hospital , Caltanissetta, Italy
| | - Endrit Shahini
- Diagnostic and Interventional Endoscopy, Candiolo Cancer Institute, FPO - IRCCS - Candiolo , Torino, Italy
| | - Fabio S Macaluso
- Internal Medicine, Villa Sofia - V. Cervello Hospital , Palermo, Italy
| | - Gaetano C Morreale
- Gastroenterology and Endoscopy Unit, S. Elia-Raimondi Hospital , Caltanissetta, Italy
| | - Emanuele Sinagra
- Gastroenterology and Endoscopy Unit, Istituto San Raffaele Giglio , Cefalù, Italy
| | - Socrate Pallio
- Digestive Diseases Endoscopy Unit, Policlinico G. Martino Hospital, University of Messina , Messina, Italy
| | - Marcello Maida
- Gastroenterology and Endoscopy Unit, S. Elia-Raimondi Hospital , Caltanissetta, Italy
| |
Collapse
|
|
45
|
de Jong ME, Gillis VELM, Derikx LAAP, Hoentjen F. No Increased Risk of Colorectal Neoplasia in Patients With Inflammatory Bowel Disease and Postinflammatory Polyps. Inflamm Bowel Dis 2020; 26:1383-1389. [PMID: 31677385 PMCID: PMC7441099 DOI: 10.1093/ibd/izz261] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Patients with inflammatory bowel disease (IBD) who have postinflammatory polyps (PIPs) may have an increased risk of developing colorectal neoplasia. Current guidelines recommend an intensified surveillance strategy in these patients, although the evidence for this recommendation is conflicting. The aim of our study was to assess whether IBD patients with PIPs are at increased risk of colorectal neoplasia. METHODS We established a retrospective cohort in a tertiary IBD center with IBD patients undergoing colorectal cancer (CRC) surveillance in the current era. We compared cumulative incidences of colorectal neoplasia since IBD diagnosis between patients with and without PIPs and corrected for confounders. Second, we compared the risk of receiving a colectomy. RESULTS In our cohort with >22 years of median follow-up, 154 of 519 patients had PIPs. PIPs were associated with extensive disease (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.61-4.42; P < 0.001) and with more severe inflammation at colonoscopy (OR, 3.54; 95% CI, 2.28-5.50; P < 0.001). After correction for confounders, the presence of PIPs was not associated with development of colorectal neoplasia (hazard ratio [HR], 1.28; 95% CI, 0.85-1.93; P = 0.24) or with development of advanced neoplasia (HR, 1.38; 95% CI, 0.52-3.68; P = 0.52). There was a higher risk of colectomy in patients with PIPs (HR, 3.41; 95% CI, 1.55-7.54; P = 0.002). CONCLUSION In this cohort, PIPs were associated with disease extent, inflammation, and higher rates of colectomy. However, the presence of PIPs was not associated with the development of neoplasia. These findings suggest that patients with PIPs may not need an intensified surveillance strategy.
Collapse
Affiliation(s)
- Michiel E de Jong
- Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands,Address correspondence to: Michiel E. de Jong, MD, Inflammatory Bowel Disease Centre, Department of Gastroenterology and Hepatology, Radboud University Medical Centre, PO Box 9101, code 455, 6500 HB Nijmegen, the Netherlands ()
| | - Veerle E L M Gillis
- Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Lauranne A A P Derikx
- Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Frank Hoentjen
- Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands
| |
Collapse
|
|
46
|
Topical application of Chlorin e6-PVP (Ce6-PVP) for improved endoscopic detection of neoplastic lesions in a murine colitis-associated cancer model. Sci Rep 2020; 10:13129. [PMID: 32753653 PMCID: PMC7403373 DOI: 10.1038/s41598-020-69570-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 05/29/2020] [Indexed: 11/08/2022] Open
Abstract
Screening colonoscopy is crucial in reducing the mortality of colorectal cancer. However, detecting adenomas against the backdrop of an inflamed mucosa (e.g. in ulcerative colitis) remains exceedingly difficult. Therefore, we aimed to improve neoplastic lesion detection by employing a fluorescence-based endoscopic approach. We used the well-established murine AOM/DSS model to induce inflammation-driven carcinogenesis in the colon. In our diagnostic approach, we evaluated Chlorin e6 polyvinylpyrrolidone (Ce6-PVP)-based fluorescence endoscopy in comparison to standard white-light endoscopy. A specialized pathologist then analyzed the histology of the detected lesions. Complementary in vitro studies were performed using human cell lines and a murine organoid system. Ce6-PVP-based fluorescence endoscopy had an improved detection rate of 100% (8/8) in detecting high-grade dysplasias and carcinomas over white-light detection alone with 75% (6/8). Trade-off for this superior detection rate was an increased rate of false positive lesions with an increase in the false discovery rate from 45% for white-light endoscopy to 81% for fluorescence endoscopy. We demonstrate in a proof-of-concept study that Ce6-PVP-based fluorescence endoscopy is a highly sensitive red flag technology to identify biopsy-worthy lesions in the colon.
Collapse
|
|
47
|
Resende RH, Ribeiro IB, de Moura DTH, Galetti F, Rocha RSDP, Bernardo WM, Sakai P, de Moura EGH. Surveillance in inflammatory bowel disease: is chromoendoscopy the only way to go? A systematic review and meta-analysis of randomized clinical trials. Endosc Int Open 2020; 8:E578-E590. [PMID: 32355874 PMCID: PMC7174005 DOI: 10.1055/a-1120-8376] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 02/04/2020] [Indexed: 12/13/2022] Open
Abstract
Background and study aims Ulcerative colitis (UC) and Crohn's disease (CD) have higher risk of colorectal cancer (CRC). Guidelines recommend dysplasia surveillance with dye-spraying chromoendoscopy (DCE). The aim of this systematic review and meta-analysis was to review all randomized clinical trials (RCTs) available and compare the efficacy of different endoscopic methods of surveillance for dysplasia in patients with UC and CD. Methods Databases searched were Medline, EMBASE, Cochrane and SCIELO/LILACS. It was estimated the risk difference (RD) for dichotomous outcomes (number of patients diagnosed with one or more dysplastic lesions, total number of dysplastic lesions diagnosed and number of dysplastic lesions detected by targeted biopsies) and mean difference for continuous outcomes (procedure time). Results This study included 17 RCTs totaling 2,457 patients. There was superiority of DCE when compared to standard-definiton white light endoscopy (SD-WLE). When compared with high-definition (HD) WLE, no difference was observed in all outcomes (number of patients with dysplasia (RD 0.06; 95 % CI [-0.01, 0.13])). Comparing other techniques, no difference was observed between DCE and virtual chromoendoscopy (VCE - including narrow-band imaging [NBI], i-SCAN and flexible spectral imaging color enhancement), in all outcomes except procedure time (mean difference, 6.33 min; 95 % CI, 1.29, 11.33). DCE required a significantly longer procedure time compared with WLE (mean difference, 7.81 min; 95 % CI, 2.76, 12.86). Conclusions We found that dye-spraying chromoendoscopy detected more patients and dysplastic lesions than SD-WLE. Although no difference was observed between DCE and HD-WLE or narrow-band imaging, the main outcomes favored numerically dye-spraying chromoendoscopy, except procedure time. Regarding i-SCAN, FICE and auto-fluorescence imaging, there is still not enough evidence to support or not their recommendation.
Collapse
Affiliation(s)
| | - Igor Braga Ribeiro
- Department of Endoscopy of Clinics Hospital of São Paulo University, São Paulo, Brazil
| | - Diogo Turiani Hourneaux de Moura
- Department of Endoscopy of Clinics Hospital of São Paulo University, São Paulo, Brazil
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States
| | - Facundo Galetti
- Department of Endoscopy of Clinics Hospital of São Paulo University, São Paulo, Brazil
| | | | | | - Paulo Sakai
- Department of Endoscopy of Clinics Hospital of São Paulo University, São Paulo, Brazil
| | | |
Collapse
|
|
48
|
Limdi JK, Picco M, Farraye FA. A review of endoscopic scoring systems and their importance in a treat-to-target approach in inflammatory bowel disease (with videos). Gastrointest Endosc 2020; 91:733-745. [PMID: 31786161 DOI: 10.1016/j.gie.2019.11.032] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 11/19/2019] [Indexed: 02/08/2023]
Abstract
Endoscopic assessment is currently the criterion standard for the diagnosis and assessment of mucosal disease activity, prognosis and monitoring for dysplasia, and assessment of response to therapy. Wider appreciation of the potential disconnect between symptoms and objective measures of disease activity and evidence that uncontrolled inflammation may lead to progressive intestinal injury and irreversible bowel damage with adverse events has led to the concept of treating to target. Treating to target is defined as treating patients with high risk for disease progression early to prevent or limit intestinal injury or disability. Endoscopic remission (mucosal healing) has emerged as a key goal of therapy. Although there are no currently validated definitions of endoscopic mucosal remission, the use of endoscopic scoring systems add uniformity and objectivity and aid standardization with reporting of mucosal appearance, augmenting clinical decision making. A plethora of scoring systems exist to define activity, response, and remission in both Crohn's disease and ulcerative colitis. In this review, we discuss the most commonly used endoscopic scoring systems and proposed definitions of response and remission, and how they can be integrated into a treat-to-target approach to optimize patient outcomes.
Collapse
Affiliation(s)
- Jimmy K Limdi
- The Pennine Acute Hospitals NHS Trust, Manchester Academic Health Sciences, University of Manchester, Manchester, United Kingdom
| | - Michael Picco
- Division of Gastroenterology and Hepatology, Inflammatory Bowel Disease Center, Mayo Clinic, Jacksonville, Florida, USA
| | - Francis A Farraye
- Division of Gastroenterology and Hepatology, Inflammatory Bowel Disease Center, Mayo Clinic, Jacksonville, Florida, USA
| |
Collapse
|
|
49
|
Pugliese N, Roda G, Peyrin-Biroulet L, Danese S. Emerging therapies for the treatment of ulcerative colitis. Expert Opin Emerg Drugs 2020; 25:1-9. [PMID: 32148112 DOI: 10.1080/14728214.2020.1737009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 02/27/2020] [Indexed: 12/16/2022]
Abstract
Introduction: Ulcerative colitis (UC) is a chronic idiopathic autoimmune inflammatory disorder, primarily affecting the gastrointestinal system. There are many patients affected that do not respond well to therapy and many others to which there is a loss of efficacy every year. The proportion of patients who have already experienced anti-TNF therapy is constantly increasing, making the development of new drugs with alternative mechanisms of action an important need for the treatment of UC.Areas covered: This review aims on emerging drugs in the treatment of UC and reviews data on their efficacy and safety.Expert opinion: UC, for many years, comparatively to CD, received little attention for several possible reasons, especially because it was not considered as a progressive disease able to induce irreversible bowel damage. This has led to lower investments by the scientific community and a slower development of therapeutic options for UC. In the past few years, this trend has started to change. In fact, new promising drugs have been developed and others are emerging with positive results. Although many treatment modalities have recently been approved, additional drugs are currently being investigated and will probably be part of the UC treatment regimen in the coming years.
Collapse
Affiliation(s)
- Nicola Pugliese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Giulia Roda
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Hepato-Gastroenterology and Inserm U954, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| |
Collapse
|
|
50
|
Verdon C, Aruljothy A, Lakatos PL, Bessissow T. Endoscopic surveillance strategies for dysplasia in ulcerative colitis. Frontline Gastroenterol 2020; 11:124-132. [PMID: 32133111 PMCID: PMC7043085 DOI: 10.1136/flgastro-2018-101056] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2018] [Revised: 03/11/2019] [Accepted: 03/17/2019] [Indexed: 02/04/2023] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disorder with an increased risk of colorectal cancer (CRC). This has led to the implementation of surveillance programmes to minimise this risk. Overall, these proactive programmes in association with better medical therapies have reduced the incidence of CRC in this population. Specific populations remain at increased risk, such as younger age at diagnosis, primary sclerosing cholangitis, colonic strictures and pseudopolyps. The majority of gastrointestinal international societies favour chromoendoscopy with targeted biopsies or random biopsies. The aim of this review is to present the current literature on dysplasia surveillance, the methodology and endoscopic technology available to assess dysplasia in UC.
Collapse
Affiliation(s)
- Christine Verdon
- Gastroenterology, McGill University Health Centre, Montreal, Québec, Canada
| | - Achuthan Aruljothy
- Gastroenterology, McGill University Health Centre, Montreal, Québec, Canada
| | - Peter L Lakatos
- Gastroenterology, McGill University Health Centre, Montreal, Québec, Canada
- 1st Department of Medicine, Semmelweis University, Budapest, Hungary
| | - Talat Bessissow
- Gastroenterology, McGill University Health Centre, Montreal, Québec, Canada
- 1st Department of Medicine, Semmelweis University, Budapest, Hungary
| |
Collapse
|