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Tukek NB, Bakkaloglu OK, Sen G, Hatemi İ, Celik AF, Erzin YZ. The effects of biologics on ulcerative colitis-related colectomy rate: results of a 22-year study. Scand J Gastroenterol 2025:1-10. [PMID: 40302309 DOI: 10.1080/00365521.2025.2497954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 02/25/2025] [Accepted: 04/22/2025] [Indexed: 05/02/2025]
Abstract
BACKGROUND To assess the impact of the biological era on colectomy rates in ulcerative colitis (UC) patients and identify factors associated with the necessity for colectomy in a large cohort from Eastern Europe. METHODS A retrospective cohort study was conducted on UC patients followed at a tertiary care center covering 1999 to 2021. Patients who underwent colectomy due to disease activity were compared to those who did not. Factors related to colectomy and the influence of the biological era were analyzed. RESULTS Among 1197 patients with a median follow-up of 3.3 years, 18% received biological agents and 5.3% underwent colectomy due to disease activity. The colectomy rate was lower in the biological era compared to the pre-biological era (2% vs. 12%; p < 0.001). Independent predictors of colectomy included steroid dependency, steroid resistance, lack of mucosal remission, and elevated CRP levels. Patients who achieved and maintained mucosal remission and had CRP levels below 3 mg/L had a significantly lower risk of colectomy. CONCLUSIONS The biological era has significantly reduced colectomy rates in UC patients. Achieving mucosal remission and maintaining low CRP levels are essential for preventing colectomy and improving long-term outcomes.
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Affiliation(s)
- Nur Beyza Tukek
- Clinic of Internal Medicine, Tekirdag Dr Ismail Fehmi Cumalioglu City Hospital, Tekirdag, Turkey
| | - Oguz Kagan Bakkaloglu
- Division of Gastroenterology, Department of Internal Medicine, Kosuyolu High Specialization Research and Education Hospital, Istanbul, Turkey
| | - Gozde Sen
- Clinic of Internal Medicine, Istanbul Bahcelievler State Hospital, Istanbul, Turkey
| | - İbrahim Hatemi
- Division of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Cerrahpasa, Istanbul, Turkey
| | - Aykut Ferhat Celik
- Division of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Cerrahpasa, Istanbul, Turkey
| | - Yusuf Ziya Erzin
- Division of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Cerrahpasa, Istanbul, Turkey
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2
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Mishra S, Sekar A, Jena A, Prasad KK, Sachan A, Singh AK, Shah J, Mandavdhare HS, Singh H, Dutta U, Sharma V. Histological scores are poor predictors of short term outcomes in acute severe ulcerative colitis: An observational study. Dig Liver Dis 2025; 57:303-307. [PMID: 39389857 DOI: 10.1016/j.dld.2024.09.014] [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: 08/27/2024] [Revised: 09/17/2024] [Accepted: 09/18/2024] [Indexed: 10/12/2024]
Abstract
BACKGROUND The role of various histologic scores in predicting outcomes in acute severe ulcerative colitis (ASUC) is unexplored. METHODS Consecutive patients of ASUC undergoing sigmoidoscopy and histological assessment by two independent pathologists for Simplified Geboes score (SGS), Robarts Histopathology Index (RHI) and Nancy histological index (NHI)] were included. Primary outcome was the role of histology in predicting need for second-line therapy or colectomy. RESULTS Of 82 patients with ASUC (mean age: 36 years, males 47.5 %), non-response to steroids was observed in 27 (32.9 %) of cases. Sixteen patients required second-line drug therapy and 8 required colectomy. There was no significant association between the need for second-line therapy or colectomy and the baseline histological scores [NHI (p = 0.61), SGS (p = 0.116) and RHI (p = 0.109)]. All three scores performed poorly to predict the need for second-line treatment or colectomy within 28 days. There was no significant association between histological scores and steroid response (NHI (p = 0.796), SGS (p = 0.57) and RHI (p = 0.941)]. All three scores had a strong positive correlation observed between each other but not with endoscopic Mayo score. CONCLUSION The three histologic scores (SGS, RHI and NHI) performed poorly in prediction of need for second-line treatment or colectomy in ASUC. Future studies should study the impact of histologic assessment on long term outcomes in ASUC.
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Affiliation(s)
- Shubhra Mishra
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Aravind Sekar
- Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Anuraag Jena
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Kaushal K Prasad
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Anurag Sachan
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Anupam Kumar Singh
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Jimil Shah
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Harshal S Mandavdhare
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Harjeet Singh
- GI Surgery, HPB and Liver Transplantation, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Usha Dutta
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Vishal Sharma
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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Kim JE, Kim M, Kim MJ, Kim ER, Hong SN, Chang DK, Ha SY, Kim YH. Histologic improvement predicts endoscopic remission in patients with ulcerative colitis. Sci Rep 2024; 14:19926. [PMID: 39198522 PMCID: PMC11358415 DOI: 10.1038/s41598-024-68372-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 07/23/2024] [Indexed: 09/01/2024] Open
Abstract
Limited research has been performed to determine if histologic improvement serves as a prognosticator for endoscopic remission, a key therapeutic target for ulcerative colitis (UC). The primary aim of the study was to evaluate if histological activity could predict endoscopic remission in UC patients with Mayo endoscopic subscores (MES) of 0 or 1. In addition, we compared the clinical outcomes between histologic improvement group and active group. This research encompassed 492 individuals with UC with MES of 0 or 1, who underwent histological assessment as per the established protocol of Samsung Medical Center between January 2018 and December 2020. Participants were categorized into two cohorts based on the degree of histological activity: those showing histologic improvement and those with ongoing histologic activity. The endoscopic activity was assessed during follow-up, and the primary outcome was endoscopic remission according to histologic activity. Out of the total participants, endoscopic activity was scrutinized in 435 patients during the colonoscopic follow-up and in 146 during the subsequent one. The histologic improvement group at the index colonoscopy was more likely achieve endoscopic remission than the histologic active group. Clinical relapse was more likely in the histologic active group than in the histologic improvement group.
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Affiliation(s)
- Ji Eun Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Minjee Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Min-Ji Kim
- Biomedical Statistics Center, Research Institute of Future Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Eun Ran Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Sung Noh Hong
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Dong Kyung Chang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Sang Yun Ha
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
| | - Young-Ho Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
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4
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Wei ZH, Wu RC, Kuo CJ, Chiu HY, Yeh PJ, Chen CM, Chiu CT, Tsou YK, Chang CW, Pan YB, Le PH. Impact of completely histological remission on reducing flare-ups in moderate-to-severe, biologics-experienced ulcerative colitis patients with endoscopic remission. J Formos Med Assoc 2024:S0929-6646(24)00352-8. [PMID: 39098580 DOI: 10.1016/j.jfma.2024.08.001] [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: 06/07/2024] [Revised: 07/29/2024] [Accepted: 08/01/2024] [Indexed: 08/06/2024] Open
Abstract
BACKGROUND/PURPOSE Endoscopic remission is presently recognized as the standard therapeutic target in the treatment of ulcerative colitis (UC). However, achieving histological remission is increasingly viewed as a pivotal objective. This study investigates the effects of attaining completely histological remission on the clinical outcomes for UC patients with a high disease burden who have already reached endoscopic remission. This is the inaugural study to concentrate on this specific patient demographic. METHODS This retrospective cohort study enrolled moderate-to-severe, biologics-experienced UC patients with completely endoscopic remission (Mayo endoscopic subscore of 0) between June 2017 and October 2023 at Chang Gung Memorial Hospital, Linkou. Patients were classified into histological remission (HR) and non-histological remission (non-HR) groups based on the Nancy index (NI). HR was defined as an NI score of 0, with all other patients categorized as non-HR. The definition of flare-ups was based on both clinical and endoscopic evidence. Comparative analyses focused on baseline characteristics and clinical outcomes at follow-up. RESULTS A total of 42 patients (HR group: 23, non-HR group: 19) were included. The average follow-up duration was 17.6 months. Baseline characteristics were comparable between the groups. At the end of follow-up, the HR group showed a significantly lower rate of acute flare-ups (26.1% vs. 68.4%, P = 0.006). Although not statistically significant, the HR group also experienced fewer emergency department visits and hospital admissions. CONCLUSIONS For moderate-to-severe, biologics-experienced UC patients in endoscopic remission, achieving completely histological remission is associated with a substantial reduction in flare-ups, suggesting its potential as a valuable therapeutic target.
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Affiliation(s)
- Zih-Hao Wei
- School of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Ren-Chin Wu
- Department of Anatomic Pathology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Chang Gung Inflammatory Bowel Disease Center, Linkou, Taoyuan, Taiwan
| | - Chia-Jung Kuo
- Chang Gung Inflammatory Bowel Disease Center, Linkou, Taoyuan, Taiwan; Chang Gung Microbiota Therapy Center, Linkou, Taoyuan, Taiwan; Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Taiwan Association for the Study of Small Intestinal Diseases (TASSID), Taoyuan, Taiwan
| | - Horng-Yih Chiu
- School of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Pai-Jui Yeh
- Chang Gung Inflammatory Bowel Disease Center, Linkou, Taoyuan, Taiwan; Chang Gung Microbiota Therapy Center, Linkou, Taoyuan, Taiwan; Division of Pediatric Gastroenterology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - Chien-Ming Chen
- Chang Gung Inflammatory Bowel Disease Center, Linkou, Taoyuan, Taiwan; Department of Medical Imaging and Interventions, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - Cheng-Tang Chiu
- Chang Gung Inflammatory Bowel Disease Center, Linkou, Taoyuan, Taiwan; Chang Gung Microbiota Therapy Center, Linkou, Taoyuan, Taiwan; Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Taiwan Association for the Study of Small Intestinal Diseases (TASSID), Taoyuan, Taiwan
| | - Yung-Kuan Tsou
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - Chen-Wang Chang
- Taiwan Association for the Study of Small Intestinal Diseases (TASSID), Taoyuan, Taiwan; Department of Gastroenterology and Hepatology, Mackay Memorial Hospital, Taipei, Taiwan
| | - Yu-Bin Pan
- Biostatistical Section, Clinical Trial Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - Puo-Hsien Le
- Chang Gung Inflammatory Bowel Disease Center, Linkou, Taoyuan, Taiwan; Chang Gung Microbiota Therapy Center, Linkou, Taoyuan, Taiwan; Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Taiwan Association for the Study of Small Intestinal Diseases (TASSID), Taoyuan, Taiwan.
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5
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Jin X, You Y, Ruan G, Zhou W, Li J, Li J. Deep mucosal healing in ulcerative colitis: how deep is better? Front Med (Lausanne) 2024; 11:1429427. [PMID: 39156693 PMCID: PMC11327023 DOI: 10.3389/fmed.2024.1429427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 07/22/2024] [Indexed: 08/20/2024] Open
Abstract
Ulcerative colitis (UC), characterized by its recurrent nature, imposes a significant disease burden and compromises the quality of life. Emerging evidence suggests that achieving clinical remission is not sufficient for long-term remission. In pursuit of a favorable prognosis, mucosal healing (MH) has been defined as the target of therapies in UC. This paradigm shift has given rise to the formulation of diverse endoscopic and histological scoring systems, providing distinct definitions for MH. Endoscopic remission (ER) has been widely employed in clinical practice, but it is susceptible to subjective factors related to endoscopists. And there's growing evidence that histological remission (HR) might be associated with a lower risk of disease flares, but the incorporation of HR as a routine therapeutic endpoint remains a debate. The integration of advanced technology has further enriched the definition of deep MH. Up to now, a universal standardized definition for deep MH in clinical practice is currently lacking. This review will focus on the definition of deep MH, from different dimensions, and analyze strengths and limitations, respectively. Subsequent multiple large-scale trials are needed to validate the concept of deep MH, offering valuable insights into potential benefits for UC patients.
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Affiliation(s)
- Xin Jin
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Yan You
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Gechong Ruan
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Weixun Zhou
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Ji Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Jingnan Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
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6
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Momayez Sanat Z, Vahedi H, Malekzadeh R, Kasaeian A, Mohammadi Ganjaroudi N, Sima A, Mansour Ghanaei F, Ghadir M, Tirgar Fakheri H, Nasseri Moghaddam S, Alatab S, Sadeghi A, Anushiravani A, Maleki I, Yazdanbod A, Vossoughinia H, Seyyedmajidi M, Naghshbandi SJ, Baniasadi N, Parhizkar B, Matinkhah S, Gheibi S, Hosseini Hemmat Abadi RS, Valizadeh Toosi S. Causes of Colectomy in Patients with Ulcerative Colitis: Findings from an Iranian National Registry. ARCHIVES OF IRANIAN MEDICINE 2024; 27:350-356. [PMID: 39072382 PMCID: PMC11316182 DOI: 10.34172/aim.28887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 06/05/2024] [Indexed: 07/30/2024]
Abstract
BACKGROUND Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) marked by rectal and colon inflammation, leading to relapsing symptoms. Its prevalence is increasing, particularly in developed nations, impacting patients' health. While its exact cause remains unclear, genetic and environmental factors are implicated, elevating the risk of colorectal cancer (CRC). Colectomy, though declining, is still performed in select UC cases, necessitating further study. METHODS We analyzed data from the Iranian Registry of Crohn's and Colitis (IRCC) to examine UC patients undergoing colectomy. We collected demographic and clinical data from 91 patients, focusing on dysplasia. Statistical analyses assessed dysplasia risk factors. RESULTS Patients with dysplasia were older at diagnosis and surgery compared to those without dysplasia. Age emerged as a significant risk factor for dysplasia in UC patients undergoing colectomy. No significant associations were found between dysplasia and other factors. CONCLUSION Age plays a crucial role in dysplasia risk among UC patients undergoing colectomy. Older age at diagnosis and surgery may indicate a higher risk of dysplasia and CRC. Clinicians should consider age when managing UC patients and implementing screening protocols. Further research with larger samples is needed to confirm these findings.
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Affiliation(s)
- Zahra Momayez Sanat
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Homayoon Vahedi
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Malekzadeh
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Kasaeian
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
- Research Center for Chronic Inflammatory Diseases, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
- Clinical Research Development Unit, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Alireza Sima
- Sasan Alborz Biomedical Research Center, Masoud Gastroenterology and Hepatology Center, Tehran, Iran
| | - Fariborz Mansour Ghanaei
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Guilan, Iran
| | - Mohammadreza Ghadir
- Gastroenterology and Hepatology Diseases Research Center, Qom University of Medical Science, Qom, Iran
| | - Hafez Tirgar Fakheri
- Gut and Liver Research Center, Non-communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Siavosh Nasseri Moghaddam
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sudabeh Alatab
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Anahita Sadeghi
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Anushiravani
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Iradj Maleki
- Gut and Liver Research Center, Non-communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Abbas Yazdanbod
- Digestive Diseases Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Hassan Vossoughinia
- Department of Gastroenterology and Hepatology, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Sayed Jalaleddin Naghshbandi
- Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Nadieh Baniasadi
- Noncommunicable Diseases Research Center, Bam University of Medical Sciences, Bam, Iran
| | - Baran Parhizkar
- Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | | | - Shahsanam Gheibi
- Maternal and Childhood Obesity Research center, Urmia University of Medical Sciences, Urmia, Iran
| | | | - Seyedmohamad Valizadeh Toosi
- Gut and Liver Research Center, Non-communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran
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Wang Z, Wang J, Yang Z, Li S, Ding C, Gong J. A specific phenotype of pouchitis was associated with worst prognosis in patients with ulcerative colitis according to Chicago classification. Dig Liver Dis 2024; 56:1007-1013. [PMID: 38065699 DOI: 10.1016/j.dld.2023.11.035] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 11/23/2023] [Accepted: 11/27/2023] [Indexed: 05/28/2024]
Abstract
BACKGROUND The impact of different pouch phenotypes on long-term functional outcomes and quality of life (QoL) remains unclear. Our aim is to investigate the association between endoscopic pouchitis phenotypes and patients' long-term prognosis by assessing pouch function and QoL. METHODS Pouchitis was classified into distinct phenotypes according to the Chicago Classification. Pouch function was assessed using the Pouch Functional Score (PFS), and QoL was evaluated using the Cleveland Global Quality of Life (CGQL) score. RESULTS A total of 252 patients were enrolled in the study, with 78 patients diagnosed with pouchitis. According to the Chicago classification, 42 of these pouchitis patients exhibited an endoscopic phenotype characterized by a combination of diffuse inflammation of the pouch body, inlet involvement, and cuffitis, referred to as the Diffuse-Inlet-Cuffitis phenotype. Patients with pouchitis of the Diffuse-Inlet-Cuffitis phenotype showed significantly higher PFS (11.5 vs 5.5, p = 0.013) and lower CGQL scores (0.67 vs 0.7, p = 0.029) compared to those with other pouch phenotypes. Independent risk factors for this severe phenotype were identified as preoperative disease duration (OR = 1.062, 95% CI: 1.006-1.122, p = 0.030) and disease extent E3 (OR = 2.836, 95% CI: 1.052-7.644, p = 0.036). CONCLUSIONS Our study suggested that pouchitis with the Diffuse-Inlet-Cuffitis endoscopic phenotype is common and seriously impairs the long-term prognosis in patients with UC after IPAA. The finding will be beneficial to the stratified management of patients with pouchitis.
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Affiliation(s)
- Zhongyuan Wang
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Jiansheng Wang
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Zirui Yang
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Song Li
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Chao Ding
- Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Jianfeng Gong
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
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8
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Vieujean S, Laharie D, Buisson A, Roblin X, Fumery M, Nancey S, Wils P, Altwegg R, Seidel L, Caron B, Peyrin-Biroulet L. Histological healing induced by tofacitinib in ulcerative colitis: A multicentre study. Dig Liver Dis 2024; 56:613-621. [PMID: 38065698 DOI: 10.1016/j.dld.2023.11.022] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 11/18/2023] [Accepted: 11/20/2023] [Indexed: 03/25/2024]
Abstract
BACKGROUND While the efficacy of tofacitinib to induce and maintain clinical and endoscopic remission is well established in ulcerative colitis (UC), little is known about its efficacy to induce histological remission. METHODS We conducted a retrospective multicentric cohort study. UC patients ≥ 16 years treated by tofacitinib in whom histological activity has been evaluated before and after induction were eligible. The primary endpoint was the histological remission at the end of induction, assessed by the Nancy index and the epithelial neutrophilic infiltrate. RESULTS A total of 42 patients with UC (93% previously exposed to an anti-TNF and 81% to vedolizumab) were included between July 2018 and April 2022 and were followed for a median duration of 84 weeks [IQR, 35-134]. At the end of induction period (whether prolonged or not), 19% and 24% of patients achieved histological remission, using the Nancy index and the epithelial neutrophilic infiltrate, respectively. Survival without tofacitinib discontinuation was significantly longer in patients without epithelial neutrophilic infiltrate at the end of induction (whether prolonged or not) compared with patients with epithelial neutrophilic infiltrate (p = 0.036). CONCLUSION Tofacitinib induced histological remission in one fifth to one quarter of patients with UC who have previously failed anti-TNF or/and vedolizumab after induction (whether prolonged or not).
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Affiliation(s)
- Sophie Vieujean
- Hepato-Gastroenterology and Digestive Oncology, University Hospital CHU of Liège, Liège, Belgium
| | - David Laharie
- CHU de Bordeaux, Centre Medico-chirurgical Magellan, Hôpital Haut-Lévêque, Gastroenterology department, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France
| | - Anthony Buisson
- Université Clermont Auvergne, Inserm, CHU Clermont-Ferrand, 3iHP, Service d'Hépato-Gastro Entérologie, Clermont-Ferrand, France
| | - Xavier Roblin
- Department of Gastroenterology, University Hospital of Saint-Etienne, Saint-Etienne, France
| | - Mathurin Fumery
- Gastroenterology Unit, Amiens University Hospital and PeriTox, Université de Picardie Jules Verne, Amiens UMR-IO1, France
| | - Stephane Nancey
- Gastroenterology Department CHU Lyon-Sud, Hospices Civils de Lyon, University Claude Bernard Lyon 1, INSERM U1111 - CIRI, Lyon, France
| | - Pauline Wils
- Univ. Lille, Inserm, CHU Lille, U1286 - Institute for Translational Research in Inflammation, Lille F-59000, France
| | - Romain Altwegg
- Hepato-gastroenterology Department, CHU Montpellier, Montpellier, France
| | - Laurence Seidel
- Biostatistics and medico-economic information department, Liège, Belgium
| | - Bénédicte Caron
- Department of Gastroenterology, Nancy University Hospital, Vandœuvre-lès-Nancy F-54500, France; INSERM, NGERE, University of Lorraine, Nancy F-54000, France; NFINY Institute, Nancy University Hospital, Vandœuvre-lès-Nancy F-54500, France; FHU-CURE, Nancy University Hospital, Vandœuvre-lès-Nancy F-54500, France
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Vandœuvre-lès-Nancy F-54500, France; INSERM, NGERE, University of Lorraine, Nancy F-54000, France; NFINY Institute, Nancy University Hospital, Vandœuvre-lès-Nancy F-54500, France; FHU-CURE, Nancy University Hospital, Vandœuvre-lès-Nancy F-54500, France; Groupe Hospitalier privé Ambroise Paré - Hartmann, Paris IBD centre, Neuilly sur Seine 92200, France; Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC, Canada.
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Scarallo L, Fioretti L, Paci M, Naldini S, Renzo S, Barp J, Gissi A, Di Paola M, Villanacci V, Lionetti P. Histological healing as a predictor of sustained clinical remission in paediatric ulcerative colitis. Dig Liver Dis 2024; 56:43-49. [PMID: 37455156 DOI: 10.1016/j.dld.2023.06.020] [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: 03/29/2023] [Revised: 06/20/2023] [Accepted: 06/22/2023] [Indexed: 07/18/2023]
Abstract
BACKGROUND The study aimed to assess the longitudinal impact of endoscopic healing (EH) and histological healing (HH) in a cohort of paediatric patients affected by ulcerative colitis (UC). METHODS This was a retrospective single-centre longitudinal study. 86 children with UC who underwent endoscopic re-assessment while in clinical and biochemical remission were included. Partial EH was defined as a Mayo Endoscopic Subscore (MES) of 1 and complete EH was defined as a MES of 0. HH was defined as the absence of active inflammation in all biopsies. The cumulative incidence of clinical relapse was evaluated during follow-up. RESULTS At the second endoscopic re-evaluation, 59 (68.6%) patients achieved EH (MES ≤1). Of these patients, 39 (66%) achieved complete EH. 20 of the 39 patients who achieved complete EH attained complete HH. Patients who achieved partial and complete EH showed higher recurrence-free survival rates compared to those who did not (p < 0.01 and p < 0.01, respectively). Amongst patients with complete EH, those who achieved complete HH had lower recurrence rates when compared to patients who still showed microscopic inflammation (p = 0.049). CONCLUSION Achievement of EH and HH is associated with fewer disease relapses, with patients achieving HH showing longer relapse-free survival rates.
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Affiliation(s)
- Luca Scarallo
- Gastroenterology and Nutrition Unit, Meyer Children Hospital IRCCS, Florence, Italy; Department of NEUROFARBA, University of Florence, Italy
| | - Lorenzo Fioretti
- Gastroenterology and Nutrition Unit, Meyer Children Hospital IRCCS, Florence, Italy
| | - Monica Paci
- Gastroenterology and Nutrition Unit, Meyer Children Hospital IRCCS, Florence, Italy
| | - Sara Naldini
- Gastroenterology and Nutrition Unit, Meyer Children Hospital IRCCS, Florence, Italy
| | - Sara Renzo
- Gastroenterology and Nutrition Unit, Meyer Children Hospital IRCCS, Florence, Italy
| | - Jacopo Barp
- Gastroenterology and Nutrition Unit, Meyer Children Hospital IRCCS, Florence, Italy
| | - Anna Gissi
- Gastroenterology and Nutrition Unit, Meyer Children Hospital IRCCS, Florence, Italy
| | - Monica Di Paola
- Gastroenterology and Nutrition Unit, Meyer Children Hospital IRCCS, Florence, Italy
| | | | - Paolo Lionetti
- Gastroenterology and Nutrition Unit, Meyer Children Hospital IRCCS, Florence, Italy; Department of NEUROFARBA, University of Florence, Italy.
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Parkes G, Ungaro RC, Danese S, Abreu MT, Arenson E, Zhou W, Ilo D, Laroux FS, Deng H, Sanchez Gonzalez Y, Peyrin-Biroulet L. Correlation of mucosal healing endpoints with long-term clinical and patient-reported outcomes in ulcerative colitis. J Gastroenterol 2023; 58:990-1002. [PMID: 37490069 PMCID: PMC10522527 DOI: 10.1007/s00535-023-02013-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Accepted: 06/20/2023] [Indexed: 07/26/2023]
Abstract
BACKGROUND We evaluated the clinical relevance of achieving histologic endoscopic mucosal improvement (HEMI) and the more stringent target of histologic endoscopic mucosal remission (HEMR) in the phase 3 maintenance trial of upadacitinib for moderately to severely active ulcerative colitis. METHODS Clinical and patient-reported outcomes were assessed in patients with clinical response after 8- or 16-week upadacitinib induction who received 52-week upadacitinib maintenance treatment. Cross-sectional and predictive analyses evaluated the relationship between HEMR or HEMI at Week 8/16 and Week 52, respectively, and outcomes at Week 52. Adjusted odds ratios (aOR) were derived from logistic regressions for patients achieving HEMR or HEMI without HEMR versus those not achieving HEMI. RESULTS Cross-sectional analyses showed that patients with HEMR had greater odds of achieving all clinical and patient-reported outcomes at Week 52 than those not achieving HEMI. In predictive analyses, patients with HEMR at Week 8/16 had significantly greater odds of achieving clinical remission (aOR = 3.6, p = 0.001) and endoscopic remission (aOR = 3.9, p < 0.001) at Week 52 than patients not achieving HEMI and HEMR. For patients achieving HEMI without HEMR, these odds were lower: clinical remission (aOR = 3.2, p < 0.001) and endoscopic remission (aOR = 2.4, p = 0.010). The odds of achieving clinically meaningful improvements in most patient-reported outcomes were directionally similar between HEMI and HEMR, but not statistically different to patients not achieving HEMI. No hospitalizations or surgeries were observed in patients with HEMR at Week 52. CONCLUSIONS Achievement of HEMR or HEMI is clinically relevant with HEMR being associated with greater likelihood of improvement in long-term clinical and patient-reported outcomes. https://www. CLINICALTRIALS gov NCT02819635.
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Affiliation(s)
- Gareth Parkes
- Dept of Gastroenterology, Royal London Hospital, Barts Health NHS Trust, London, UK.
| | - Ryan C Ungaro
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy
| | - Maria T Abreu
- Division of Gastroenterology, Crohn's and Colitis Center, University of Miami Miller School of Medicine, Miami, FL, USA
| | | | | | | | | | - Huiwen Deng
- AbbVie Inc., Chicago, IL, USA
- Department of Pharmacy Systems Outcomes and Policy, University of Illinois at Chicago, Chicago, IL, USA
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11
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Pudipeddi A, Fung C, Christensen B, Bryant RV, Subramaniam K, Chetwood J, Paramsothy S, Leong RW. Knowledge and attitudes towards the use of histological assessments in ulcerative colitis by gastroenterologists vs pathologists. World J Gastroenterol 2023; 29:378-389. [PMID: 36687119 PMCID: PMC9846936 DOI: 10.3748/wjg.v29.i2.378] [Citation(s) in RCA: 4] [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: 09/11/2022] [Revised: 11/04/2022] [Accepted: 12/23/2022] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Histological remission is increasingly accepted as a treatment endpoint in the management of ulcerative colitis (UC). However, the knowledge of histology guidelines and the attitudes towards their use in clinical practice by gastroenterologists and pathologists is unknown.
AIM To evaluate the knowledge of histology guidelines and attitudes towards the use of histology in UC by gastroenterologists and pathologists.
METHODS A prospective, cross-sectional nationwide survey of gastroenterologists and pathologists who analyse UC specimens was conducted. The survey consisted of 34 questions to assess gastroenterologists’ and pathologists’ knowledge (score out of 19) and attitudes towards histological assessment in UC. Survey questions were formulated using the European Crohn’s and Colitis position paper on histopathology and the British Society of Gastroenterology biopsy reporting guidelines. It included knowledge of histological assessment of disease activity and dysplasia, knowledge of histological scoring systems for ulcerative colitis, uptake of histology scoring systems in routine practice, attitudes towards the role of histological activity, and the use of histological activity in clinical scenarios.
RESULTS Of 89 responders (77 gastroenterologists, 12 pathologists), there was almost universal acceptance that histological assessment should form part of UC evaluation [95% gastroenterologists, 92% pathologists]. However, gastroenterologists reported that 92% of their pathologists do not use a histological scoring system. Utilisation of a formal histological scoring system was preferred by 77% of gastroenterologists and 58% of pathologists. Both groups lacked awareness of the Geboes Score, Nancy Index and Robarts Histopathological Index scoring systems with 91%, 87%, and 92% of gastroenterologists respectively; and 83%, 83%, and 92% pathologists respectively, being uncertain of scoring systems’ remission definitions. Histology knowledge score was not significantly different between gastroenterologists and pathologists [9/19 (IQR: 8-11) vs 8/19 (IQR: 7-10), P = 0.54]. Higher knowledge scores were predicted by hospital attending gastroenterologists (P = 0.004), participation in inflammatory bowel disease (IBD) multidisciplinary teams (P = 0.009), and self-declared IBD sub-specialist (P = 0.03).
CONCLUSION Histological remission is a recognised target for both gastroenterologists and pathologists. Despite this, knowledge of histological scoring systems and their utilisation is poor.
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Affiliation(s)
- Aviv Pudipeddi
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney 2139, Australia
- Faculty of Medicine and Health, Concord Clinical School, University of Sydney, Sydney 2138, Australia
| | - Caroline Fung
- Department of Anatomical Pathology, Concord Repatriation General Hospital, Sydney 2139, Australia
| | - Britt Christensen
- Department of Gastroenterology, Royal Melbourne Hospital, Melbourne 3050, Australia
- Department of Medicine, University of Melbourne, Melbourne 3052, Australia
| | - Robert V Bryant
- Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Adelaide 5011, Australia
| | - Kavitha Subramaniam
- Gastroenterology and Hepatology Unit, Canberra Hospital, Canberra 2605, Australia
- Australian National University Medical School, Australian National University, Canberra 2601, Australia
| | - John Chetwood
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney 2139, Australia
| | - Sudarshan Paramsothy
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney 2139, Australia
- Faculty of Medicine and Health, Concord Clinical School, University of Sydney, Sydney 2138, Australia
- Faculty of Medicine and Health Sciences, Macquarie University Hospital, Sydney 2109, Australia
| | - Rupert W Leong
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney 2139, Australia
- Faculty of Medicine and Health, Concord Clinical School, University of Sydney, Sydney 2138, Australia
- Faculty of Medicine and Health Sciences, Macquarie University Hospital, Sydney 2109, Australia
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Ileoanal Pouch Syndrome Is Common and Associated With Significant Disability in Patients With Ulcerative Colitis Undergoing IPAA. Dis Colon Rectum 2022; 65:1503-1513. [PMID: 36382841 DOI: 10.1097/dcr.0000000000002439] [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] [Indexed: 11/17/2022]
Abstract
BACKGROUND Recently, ileoanal pouch syndrome (IPS) has been proposed and defined according to a series of patient-centered bowel symptoms and consequences after ileoanal pouch surgery. OBJECTIVE The purpose of this study was to investigate the prevalence of IPS and the related disability in UC patients undergoing IPAA. DESIGN This was a cross-sectional study. SETTING This study was conducted in a tertiary center. PATIENTS Data of 128 UC-related IPAA from October 2014 to May 2021 were collected. MAIN OUTCOME MEASURES Primary outcomes were prevalence of IPS. RESULTS One hundred twenty-eight patients were enrolled with a median postoperative follow-up of 2.64 (IQR, 1.31-3.80) years. The prevalence of IPS and its constituent symptoms and consequences are lower for patients with longer follow-up after ileostomy reversal. Fecal incontinence and pad usage had the greatest impact on the quality of life affecting 29% and 31% of patients. IPS group had a significantly higher IBD-Disability Index score compared to the non-IPS group (27.25 vs 12.15, p < 0.001). Multivariate analysis showed that 4 symptoms (fecal incontinence, clustering, fragmentation and incomplete evacuation, and nocturnal symptoms) and 2 consequences (pad usage and negative mental alterations) were associated with increased IBD-Disability Index (p < 0.05). For patients followed-up for >2 years, multivariate analysis showed that male gender (OR, 4.485; 95% CI, 1.354-14.857; p = 0.014), preoperative duration of disease (OR, 1.013; 95% CI, 1.001-1.025; p = 0.031), and postoperative follow-up (OR, 0.462; 95% CI, 0.244-0.876; p = 0.049) were independently associated with IPS. LIMITATIONS This is a single-center cross-sectional study rather than a prospective multicenter large longitudinal study. CONCLUSIONS IPS is a common situation negatively affecting the quality of life for patients with ulcerative colitis undergoing IPAA, and its rate decreased over time from ileal pouch surgery. See Video Abstract at http://links.lww.com/DCR/C41. EL SNDROME DEL RESERVORIO ILEOANAL ES COMN Y EST ASOCIADO CON UNA DISCAPACIDAD SIGNIFICATIVA EN PACIENTES CON CU CON RESERVORIO ILEAL Y ANASTOMOSIS RESERVORIOANAL ANTECEDENTES:Recientemente se propuso y definió el síndrome del reservorio ileoanal de acuerdo con una serie de síntomas intestinales centrados en el paciente y las consecuencias después de la cirugía del reservorio ileoanal.OBJETIVO:El propósito de este estudio fue investigar la prevalencia del síndrome del reservorio ileoanal y la discapacidad relacionada en pacientes con colitis ulcerosa con reservorio ileal y anastomosis reservorio-anal.DISEÑO:Este fue un estudio transversal.ESCENARIO:Este estudio se realizó en un centro terciario.PACIENTES:Se recopilaron datos de 128 pacientes con reservorio ileal por colitis ulcerosa desde octubre de 2014 hasta mayo de 2021.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados primarios fueron la prevalencia del síndrome del reservorio ileoanal.RESULTADOS:Ciento veintiocho pacientes fueron reclutados con una mediana de seguimiento postoperatorio de 2,64 (IQR, 1,31-3,80) años. La prevalencia del síndrome del reservorio ileoanal y sus síntomas y consecuencias constituyentes es menor para los pacientes con un seguimiento más prolongado después de la reversión de la ileostomía. La incontinencia fecal y el uso de compresas tuvieron el mayor impacto en la calidad de vida, afectando al 29% y al 31% de los pacientes. El grupo con síndrome del reservorio ileoanal tuvo una puntuación del índice de discapacidad por enfermedad inflamatoria intestinal significativamente más alta en comparación con el grupo sin síndrome del reservorio ileoanal (27,25 frente a 12,15, p <0,001). El análisis multivariado mostró que 4 síntomas (incontinencia fecal, agrupamiento, fragmentación y evacuación incompleta y síntomas nocturnos) y 2 consecuencias (uso de toallas higiénicas y alteraciones mentales negativas) se asociaron con un aumento del índice de discapacidad por enfermedad inflamatoria intestinal (p <0,05). Para los pacientes seguidos durante más de dos años, el análisis multivariado mostró que el sexo masculino (OR, 4,485; IC 95%, 1,354-14,857; p = 0,014), la duración preoperatoria de la enfermedad (OR, 1,013; IC 95%, 1,001-1,025; p = 0,031) y el seguimiento postoperatorio (OR, 0,462; IC 95%, 0,244-0,876; p = 0,049) se asociaron de forma independiente con el síndrome del reservorio ileoanal.LIMITACIONES:Este es un estudio transversal de un solo centro en lugar de un gran estudio longitudinal prospectivo multicéntrico.CONCLUSIONES:El síndrome del reservorio ileoanal es una situación común que afecta negativamente la calidad de vida de los pacientes con colitis ulcerosa sometidos a anastomosis del reservorio ileal-anal, y su tasa disminuyó con el tiempo a partir de la cirugía del reservorio ileal. El sexo masculino y la mayor duración preoperatoria de la enfermedad son factores de riesgo importantes para el síndrome del reservorio ileoanal. Consulte Video Resumen en http://links.lww.com/DCR/C41. (Traducción-Dr. Felipe Bellolio).
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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.
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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
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Luther JP, Fritz CD, Fanous E, Waken R, Hammond JG, Joynt Maddox KE. The Association of Race, Ethnicity, and Insurance Status With Outcomes in Hospitalized Patients With Ulcerative Colitis. GASTRO HEP ADVANCES 2022; 1:985-992. [PMID: 39131255 PMCID: PMC11307435 DOI: 10.1016/j.gastha.2022.07.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 07/19/2022] [Indexed: 08/13/2024]
Abstract
Background and Aims The impact of sociodemographic factors on outcomes in patients with ulcerative colitis (UC) is not well studied. We characterized the association of race/ethnicity and insurance status with procedures, length of stay (LOS), mortality, and cost of care in a cohort of hospitalized patients with UC. Methods Data from the National Inpatient Sample from 2016 to 2018 were used. Outcomes were analyzed using generalized estimating equations. All models included age, sex, income quartile, hospital diagnosis, hospital characteristics, and Elixhauser Comorbidity Index as well as the primary predictors. Results A total of 34,814 patients were included. Black (adjusted odds ratio [aOR] 0.46, 95% confidence interval [0.39-0.55]) or Hispanic (aOR 0.74, [0.64-0.86]) patients had lower odds of colectomy than White patients. Patients with Medicare (aOR 0.54, [0.48-0.62), Medicaid (aOR 0.51, [0.45-0.58]), or no insurance (aOR 0.42, [0.35-0.50]) had lower odds of colectomy than privately insured patients. Black patients had higher mortality than White patients (aOR 1.38, [1.07-1.78]). Patients with Medicare or Medicaid had 5% ([1.01-1.09]) and 9% longer LOS ([1.05-1.13]), respectively, than privately insured patients, while uninsured patients had a 6% shorter LOS ([0.90-0.97]). Hispanic or Asian/Native American patients had 11% ([1.06-1.15]) and 13% ([1.07-1.20]) higher costs, respectively, than White patients. Uninsured patients had 11% lower hospitalization costs than privately insured patients ([0.85-0.94]). Conclusion Hospitalized patients with UC differed significantly in rates of colectomy, mortality, LOS, and costs based on race/ethnicity and insurance status. Further research is needed to understand the cause of these differences and develop targeted solutions to reduce these inequities.
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Affiliation(s)
- Janki P. Luther
- Division of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri
| | - Cassandra D.L. Fritz
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri
| | - Erika Fanous
- Division of Cardiology, Washington University School of Medicine, St. Louis, Missouri
| | - R.J. Waken
- Division of Cardiology, Washington University School of Medicine, St. Louis, Missouri
| | - J. Gmerice Hammond
- Division of Cardiology, Washington University School of Medicine, St. Louis, Missouri
| | - Karen E. Joynt Maddox
- Division of Cardiology, Washington University School of Medicine, St. Louis, Missouri
- Center for Health Economics and Policy, Institute for Public Health at Washington University, St. Louis, Missouri
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15
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Ge C, Lu Y, Shen H, Zhu L. Monitoring of intestinal inflammation and prediction of recurrence in ulcerative colitis. Scand J Gastroenterol 2022; 57:513-524. [PMID: 34994661 DOI: 10.1080/00365521.2021.2022193] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background and objectives: Ulcerative colitis is a chronic recurrent intestinal inflammatory disease, and its recurrence is difficult to predict. In this review, we summarized the objective indicators that can be used to evaluate intestinal inflammation, the purpose is to better predict the clinical recurrence of UC, formulate individualized treatment plan during remission of UC, and improve the level of diagnosis and treatment of UC.Methods: Based on the search results in the PUBMED database, we explored the accuracy and value of these methods in predicting the clinical recurrence of UC from the following three aspects: endoscopic and histological scores, serum biomarkers and fecal biomarkers.Results: Colonoscopy with biopsy is the gold standard for assessing intestinal inflammation, but it is invasive, inconvenient and expensive. At present, there is no highly sensitive and specific endoscopic or histological score to predict the clinical recurrence of UC. Compared with serum biomarkers, fecal biomarkers have higher sensitivity and specificity because they are in direct contact with the intestine and are closer to the site of intestinal inflammation. Fecal calprotectin is currently the most studied and meaningful fecal biomarker. Lactoferrin and S100A12, as novel biomarkers, have no better performance than FC in predicting the recurrence of UC.Conclusions: FC is currently the most promising predictive marker, but it lacks an accurate cut-off value. Combining patient symptoms, incorporating multiple indicators to construct a UC recurrence prediction model, and formulating individualized treatment plans for high recurrence risk patients will be the focus of UC remission management.
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Affiliation(s)
- Changchang Ge
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Yi Lu
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Hong Shen
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Lei Zhu
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
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Ferretti F, Cannatelli R, Monico MC, Maconi G, Ardizzone S. An Update on Current Pharmacotherapeutic Options for the Treatment of Ulcerative Colitis. J Clin Med 2022; 11:jcm11092302. [PMID: 35566428 PMCID: PMC9104748 DOI: 10.3390/jcm11092302] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 04/10/2022] [Accepted: 04/18/2022] [Indexed: 12/17/2022] Open
Abstract
The main goals of Ulcerative Colitis (UC) treatment are to both induce and maintain the clinical and endoscopic remission of disease, reduce the incidence of complications such as dysplasia and colorectal carcinoma and improve quality of life. Although a curative medical treatment for UC has not yet been found, new therapeutic strategies addressing specific pathogenetic mechanisms of disease are emerging. Notwithstanding these novel therapies, non-biological conventional drugs remain a mainstay of treatment. The aim of this review is to summarize current therapeutic strategies used as treatment for ulcerative colitis and to briefly focus on emerging therapeutic strategies, including novel biologic therapies and small molecules. To date, multiple therapeutic approaches can be adopted in UC and the range of available compounds is constantly increasing. In this era, the realization of well-designed comparative clinical trials, as well as the definition of specific therapeutic models, would be strongly suggested in order to achieve personalized management for UC patients.
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17
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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.
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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
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Panés J, Lindsay JO, Teich N, Lindgren S, Colombel JF, Flynn HA, Huyck S, Yao R, Philip G, Reinisch W. Colectomy Incidence Rates in Five-Year Data From the Observational Postmarketing Ulcerative Colitis Study of Originator Infliximab. Inflamm Bowel Dis 2021; 27:1963-1967. [PMID: 33577644 DOI: 10.1093/ibd/izab026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Indexed: 12/09/2022]
Abstract
BACKGROUND This analysis of the Observational Postmarketing Ulcerative Colitis Study examined incidence rates of colectomy in patients with ulcerative colitis who received originator infliximab (IFX) or conventional therapies (ConvRx) as per their treating physician. METHODS Cox proportional hazards models compared time to colectomy for both treatment groups. A secondary analysis examined colectomy incidence rates based on IFX exposure timing (defined by a 90-day window after the last IFX dose date). RESULTS Of 2239 patients with data, 1059 enrolled in IFX and 1180 enrolled in ConvRx (including 296 patients who switched to IFX). Patients in the IFX group had more severe disease at baseline vs the ConvRx group (percentage with baseline partial Mayo score 7-9: 46.0% vs 30.5%, respectively). During 5 years of follow-up, 271 patients (12.1% of enrolled patients) had colectomy. Enrollment in the IFX group was associated with a higher risk of colectomy (hazard ratio = 3.12; 95% confidence interval, 2.25-4.34; P < 0.001) compared with enrollment in the ConvRx group. A total of 174 colectomies occurred in the IFX group, but 97 of these colectomies occurred ≥90 days after the last IFX dose date. CONCLUSIONS Colectomy was reported at a higher rate in the IFX group than in the ConvRx group, although patients in the IFX group had more severe disease at baseline and most of the colectomies occurred after patients had been off of IFX for ≥90 days.
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Affiliation(s)
- Julián Panés
- Hospital Clinic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
| | - James O Lindsay
- The Royal London, Barts Health NHS Trust, London, United Kingdom
| | - Niels Teich
- Internistische Gemeinschaftspraxis, Leipzig, Germany.,Faculty of Medicine, Jena University, Jena, Germany
| | | | | | | | - Susan Huyck
- Merck & Co., Inc., Kenilworth, New Jersey, USA
| | - Ruji Yao
- Merck & Co., Inc., Kenilworth, New Jersey, USA
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Lang-Schwarz C, Angeloni M, Agaimy A, Atreya R, Becker C, Dregelies T, Danese S, Fléjou JF, Gaßler N, Grabsch HI, Hartmann A, Kamarádová K, Kühl AA, Lauwers GY, Lugli A, Nagtegaal I, Neurath MF, Oberhuber G, Peyrin-Biroulet L, Rath T, Riddell R, Rubio CA, Sheahan K, Siegmund B, Tilg H, Villanacci V, Westerhoff M, Ferrazzi F, Vieth M. Validation of the 'Inflammatory Bowel Disease-Distribution, Chronicity, Activity [IBD-DCA] Score' for Ulcerative Colitis and Crohn´s Disease. J Crohns Colitis 2021; 15:1621-1630. [PMID: 33773497 PMCID: PMC8495487 DOI: 10.1093/ecco-jcc/jjab055] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Histological scoring plays a key role in the assessment of disease activity in ulcerative colitis [UC] and is also important in Crohn´s disease [CD]. Currently, there is no common scoring available for UC and CD. We aimed to validate the Inflammatory Bowel Disease [IBD]-Distribution [D], Chronicity [C], Activity [A] score [IBD-DCA score] for histological disease activity assessment in IBD. METHODS Inter- and intra-rater reliability were assessed by 16 observers on biopsy specimens from 59 patients with UC and 25 patients with CD. Construct validity and responsiveness to treatment were retrospectively evaluated in a second cohort of 30 patients. RESULTS Inter-rater reliability was moderate to good for the UC cohort (intraclass correlation coefficients [ICCs] = 0.645, 0.623, 0.767 for D, C, and A, respectively) and at best moderate for the CD cohort [ICC = 0.690, 0.303, 0.733 for D, C, and A, respectively]. Intra-rater agreement ranged from good to excellent in both cohorts. Correlation with the Nancy Histological Index [NHI] was moderate and strong with the Simplified Geboes Score [SGS] and a Visual Analogue Scale [VAS], respectively. Large effect sizes were obtained for all three parameters. External responsiveness analysis revealed correlated changes between IBD-DCA score and NHI, SGS and VAS. CONCLUSIONS The IBD-DCA score is a simple histological activity score for UC and CD, agreed and validated by a large group of IBD specialists. It provides reliable information on treatment response. Therefore, it has potential value for use in routine diagnostics as well as clinical studies.
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Affiliation(s)
| | - Miriam Angeloni
- Institute of Pathology, Friedrich-Alexander-University, Erlangen, Germany
| | - Abbas Agaimy
- Institute of Pathology, Friedrich-Alexander-University, Erlangen, Germany
| | - Raja Atreya
- Department of Medicine & Deutsches Zentrum Immuntherapie DZI, University Hospital, Friedrich-Alexander-University, Erlangen, Germany
- Transregio 241 IBDome Consortium, Erlangen, Berlin, Germany
| | - Christoph Becker
- Department of Medicine & Deutsches Zentrum Immuntherapie DZI, University Hospital, Friedrich-Alexander-University, Erlangen, Germany
- Transregio 241 IBDome Consortium, Erlangen, Berlin, Germany
| | | | - Silvio Danese
- Department of Gastroenterology, Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Jean-François Fléjou
- Pathology Department, Saint-Antoine Hospital, Pierre et Marie Curie University, Paris, France
| | - Nikolaus Gaßler
- Institute for Legal Medicine, Section Pathology, University Hospital, Jena, Germany
| | - Heike I Grabsch
- Department of Pathology, School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands
- Pathology and Data Analytics, Leeds Institute of Medical Research at St James’s, University of Leeds, Leeds, UK
| | - Arndt Hartmann
- Institute of Pathology, Friedrich-Alexander-University, Erlangen, Germany
| | - Kateřina Kamarádová
- Fingerland Department of Pathology, Charles University Faculty of Medicine and University Hospital, Hradec Králové, Czech Republic
| | - Anja A Kühl
- Charité ‐ Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Transregio 241 IBDome Consortium, Erlangen, Berlin, Germany
| | | | | | - Iris Nagtegaal
- Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Markus F Neurath
- Department of Medicine & Deutsches Zentrum Immuntherapie DZI, University Hospital, Friedrich-Alexander-University, Erlangen, Germany
- Transregio 241 IBDome Consortium, Erlangen, Berlin, Germany
| | - Georg Oberhuber
- Institute of Pathology, Tirol Kliniken, Innsbruck, Austria
- Institute of Pathology, Patho im Zentrum, St. Pölten, Austria
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Lorraine University, Vandoeuvre, France
| | - Timo Rath
- Department of Medicine & Deutsches Zentrum Immuntherapie DZI, University Hospital, Friedrich-Alexander-University, Erlangen, Germany
| | - Robert Riddell
- Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
| | - Carlos A Rubio
- Department of Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden
| | - Kieran Sheahan
- Department of Pathology & Centre for Colorectal Disease, St Vincent´s University Hospital and University College, Dublin, Ireland
| | - Britta Siegmund
- Medical Department [Gastroenterology, Infectiology, Rheumatology], Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Transregio 241 IBDome Consortium, Erlangen, Berlin, Germany
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University Innsbruck, Innsbruck, Austria
| | | | - Maria Westerhoff
- Department of Pathology, University of Michigan, Ann Arbor, MI, USA
| | - Fulvia Ferrazzi
- Institute of Pathology, Friedrich-Alexander-University, Erlangen, Germany
- Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Michael Vieth
- Institute of Pathology, Klinikum Bayreuth GmbH, Bayreuth, Germany
- Institute of Pathology, Friedrich-Alexander-University, Erlangen, Germany
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20
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Alborzi F, Ebrahimi Daryani N, Deihim T, Azizi Z, Azmoudeh Ardalan F, Teimouri A, Taslimi R, Roshan N, Mami M, Mirzade M, Aletaha N. Colonic Mucosal Infiltration of IgG4 Plasma Cells and Ulcerative Colitis: Determinant of Presence, Activity, Extension, and Duration of Disease. Middle East J Dig Dis 2021; 13:287-293. [PMID: 36606008 PMCID: PMC9489443 DOI: 10.34172/mejdd.2021.237] [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: 01/21/2021] [Accepted: 06/11/2021] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Infiltration of IgG4 positive plasma cells has been detected in the colonic mucosa of patients with ulcerative colitis (UC). The aim of the study was to investigate the association between colonic mucosal infiltration of IgG4 plasma cells and the presence, activity, extension, and duration of UC. METHODS In this case-control study (2009-2014), 102 subjects (84 with UC/18 controls) were enrolled. Clinical records and rectosigmoid biopsies of UC patients were selected, and biopsies were stained with IgG4 monoclonal antibodies. IgG4 positive plasma cells were counted by a single pathologist. RESULTS Amongst 84 patients with UC, 73.8% had UC without primary sclerosing cholangitis (PSC), and 26.2% had UC with PSC. IgG4 plasma cells were seen in 35 (41.7%) patients with UC and 0% of controls (p = 0.001). The mean amount of IgG4 containing plasma cells was significantly different between active and inactive patients with UC, although it was not significantly different between UC patients with and without PSC. The presence of IgG4 infiltration was significantly associated with the extension and duration of the disease. Furthermore, IgG4 count had a sensitivity/specificity of 78.6%/83.3% for the diagnosis of UC. CONCLUSION Our study revealed the diagnostic role of IgG4 plasma cells in the colonic mucosa of patients with UC and its association with activity, extension, and duration of disease.
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Affiliation(s)
- Foroogh Alborzi
- Assistant Professor of Gastroenterology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Nasser Ebrahimi Daryani
- Professor of Gastroenterology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Tina Deihim
- Internal Medicine Resident, Internal Medicine Department, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Azizi
- Researcher, Iran University of Medical Sciences, Tehran, Iran
| | | | - Azam Teimouri
- Assistant Professor of Gastroenterology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Reza Taslimi
- Assistant Professor of Gastroenterology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Nader Roshan
- Associate Professor of Gastroenterology, Tehran University of Medical Sciences, Tehran, Iran
| | - Masood Mami
- Assistant Professor of Gastroenterology, Ilam University of Medical Sciences, Ilam, Iran
| | - Monirsadat Mirzade
- Resident of Community Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Najmeh Aletaha
- Associate Professor of Gastroenterology, Tehran University of Medical Sciences, Tehran, Iran
,Corresponding Author: Najmeh Aletaha,MD Gastroentrology and Hepatology Ward, Imam Khomeini Hospital, Tehran university of Medical Science, Tehran, Iran Tel: + 98 21 88799446 Fax: + 98 21 88799840
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21
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Byrne LW, McKay D. Does perioperative biological therapy increase 30-day post-operative complication rates in inflammatory bowel disease patients undergoing intra-abdominal surgery? A systematic review. Surgeon 2021; 19:e153-e167. [PMID: 34581275 DOI: 10.1016/j.surge.2020.09.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 06/29/2020] [Accepted: 09/06/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Biopharmaceuticals revolutionised inflammatory bowel disease (IBD) treatment. However, it is postulated they compromise immunity, collagen production and angiogenesis resulting in infective post-operative complications and altered wound/anastomotic healing. Research has failed to agree on risks associated with perioperative biologics therefore it was anticipated that a systematic review may provide a consensus and contribute recommendations for clinical practice. METHODS A systematic review conducted as per PRISMA guidelines included a methodical search of PubMed, Google Scholar, EMBASE/Ovid and Cochrane Library using MeSH and/or keywords for papers published between 01/01/1998 and 04/02/2019.The population analysed included adult ulcerative colitis, Crohn's disease, Indeterminate Colitis or IBD unclassified patients. The intervention was intra-abdominal surgery in patients treated with biological therapy in the preceding 12 weeks compared to patients who had intra-abdominal surgery without biological therapy within the defined timeframe. The primary outcome was surgical site infection (SSI) with secondary outcomes including wound dehiscence, intra-abdominal sepsis/abscess, systemic infection and anastomotic breakdown within 30 days post-procedure. Papers were evaluated by two independent reviewers and those included were assessed for quality/bias using the Newcastle-Ottowa scale. RESULTS 2064 UC, Crohn's and IC patients were analysed across 8 included studies. Several studies' multivariate analyses demonstrated corticosteroids to be independent predictors of morbidity. There are no increased complications associated with anti-TNFα exposure while vedolizumab increased SSI and small bowel obstruction. CONCLUSION Prospective studies and randomised control trials are required to clarify study outcomes and recommendations published to date. Presently, biologics should continue to be used and considered beneficial in this population.
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Affiliation(s)
| | - Damian McKay
- Craigavon Area Hospital, 68 Lurgan Rd, Portadown, Craigavon, BT63 5QQ, UK
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22
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Yarlas A, Willian MK, Nag A. The impact of clinical symptoms and endoscopic and histologic disease activity on health-related quality of life in patients with ulcerative colitis following treatment with multimatrix mesalazine. Qual Life Res 2021; 30:1925-1938. [PMID: 33651279 PMCID: PMC8233235 DOI: 10.1007/s11136-021-02787-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/02/2021] [Indexed: 10/28/2022]
Abstract
PURPOSE Studies of patients with ulcerative colitis (UC) report that reduced clinical symptoms and endoscopic activity predict better health-related quality of life (HRQoL). However, no study has examined the joint and unique associations of clinical and endoscopic activity with HRQoL, nor of histologic inflammation and HRQoL. These post hoc analyses evaluated whether reduced clinical, endoscopic, and histologic disease activity were uniquely associated with improved HRQoL for adults with active mild-to-moderate UC receiving once-daily 4.8 g/day multimatrix mesalazine for 8 weeks. METHODS Assessments at baseline and week 8 (i.e., treatment completion) included clinical and endoscopic activity (modified UC-Disease Activity Index), histology (Geboes scoring), and HRQoL (Short Inflammatory Bowel Disease Questionnaire [SIBDQ]; SF-12v2® Health Survey [SF-12v2]). Associations among each type of disease activity and HRQoL were examined by correlations and by mean changes in SIBDQ and SF-12v2 scores between disease activity subgroups (e.g., achievement of clinical remission; mucosal healing). Regression models estimated unique variance in HRQoL accounted by each type of disease activity. RESULTS Within the analysis sample (n = 717), patients with reduced clinical and endoscopic activity had significantly larger improvements in all HRQoL domains (p < 0.001), as did patients in both endoscopic and clinical remission compared to patients in endoscopic remission only (p < 0.05). Patients with histologic activity post-treatment scored significantly worse on all HRQoL domains than patients with no activity (p < 0.05). Correlations and regression models found that decreases in clinical and endoscopic activity were associated with improvements in HRQoL domain scores. CONCLUSIONS Clinical symptoms and mucosal health have separable, distinct impacts on UC patients' HRQoL.
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Affiliation(s)
- Aaron Yarlas
- QualityMetric, 1301 Atwood Avenue, Suite 216E, Johnston, RI, 02919, USA.
| | | | - Arpita Nag
- Shire, 300 Shire Way, Lexington, MA, 02421, USA
- Sanofi, 270 Albany St, Cambridge, MA, 02139, USA
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23
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Lang-Schwarz C, Agaimy A, Atreya R, Becker C, Danese S, Fléjou JF, Gaßler N, Grabsch HI, Hartmann A, Kamarádová K, Kühl AA, Lauwers GY, Lugli A, Nagtegaal I, Neurath MF, Oberhuber G, Peyrin-Biroulet L, Rath T, Riddell R, Rubio CA, Sheahan K, Tilg H, Villanacci V, Westerhoff M, Vieth M. Maximizing the diagnostic information from biopsies in chronic inflammatory bowel diseases: recommendations from the Erlangen International Consensus Conference on Inflammatory Bowel Diseases and presentation of the IBD-DCA score as a proposal for a new index for histologic activity assessment in ulcerative colitis and Crohn's disease. Virchows Arch 2021; 478:581-594. [PMID: 33373023 PMCID: PMC7973393 DOI: 10.1007/s00428-020-02982-7] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 11/13/2020] [Accepted: 12/01/2020] [Indexed: 12/13/2022]
Grants
- TRR241 projects INF, A03, C02, C03, C04 Deutsche Forschungsgemeinschaft
- TRR241 projects INF, A03, C02, C03 and C04 Deutsche Forschungsgemeinschaft
- TRR241 projects INF, A03,C02, C03 and C04 Deutsche Forschungsgemeinschaft
- Heisenberg Professorship Deutsche Forschungsgemeinschaft
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Affiliation(s)
- Corinna Lang-Schwarz
- Institute of Pathology, Klinikum Bayreuth GmbH, Preuschwitzer Str. 101, 95445, Bayreuth, Germany
| | - Abbas Agaimy
- Institute of Pathology, Friedrich-Alexander University, Erlangen, Germany
| | - Raja Atreya
- Medical Clinic 1, Department of Medicine & Deutsches Zentrum Immuntherapie DZI, University Hospital, Friedrich-Alexander University, Erlangen, Germany
- The Transregio 241 IBDome Consortium, Erlangen, Germany
| | - Christoph Becker
- Medical Clinic 1, Department of Medicine & Deutsches Zentrum Immuntherapie DZI, University Hospital, Friedrich-Alexander University, Erlangen, Germany
- The Transregio 241 IBDome Consortium, Erlangen, Germany
| | - Silvio Danese
- Department of Gastroenterology, IBD Centre, Humanitas Research Hospital, Via A. Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Jean-François Fléjou
- Pathology Department, Saint-Antoine Hospital, APHP, Sorbonne University, Paris, France
| | - Nikolaus Gaßler
- Institute for Legal Medicine, Section Pathology, University Hospital, Jena, Germany
| | - Heike I Grabsch
- Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands
- Pathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
| | - Arndt Hartmann
- Institute of Pathology, Friedrich-Alexander University, Erlangen, Germany
| | - Kateřina Kamarádová
- The Fingerland Department of Pathology, Faculty of Medicine and University Hospital, Charles University, Hradec Králové, Czech Republic
| | - Anja A Kühl
- The Transregio 241 IBDome Consortium, Erlangen, Germany
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, iPATH.Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany
| | | | | | - Iris Nagtegaal
- Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Markus F Neurath
- Medical Clinic 1, Department of Medicine & Deutsches Zentrum Immuntherapie DZI, University Hospital, Friedrich-Alexander University, Erlangen, Germany
- The Transregio 241 IBDome Consortium, Erlangen, Germany
| | - Georg Oberhuber
- INNPATH, Institute of Pathology, Tirol Kliniken, Innsbruck, Austria & Patho im Zentrum, St. Pölten, Austria
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Vandoeuvre, France & Inserm U1256, Lorraine University, Vandoeuvre, France
| | - Timo Rath
- Medical Clinic 1, Department of Medicine & Deutsches Zentrum Immuntherapie DZI, University Hospital, Friedrich-Alexander University, Erlangen, Germany
| | - Robert Riddell
- Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
| | - Carlos A Rubio
- Department of Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden
| | - Kieran Sheahan
- Department of Pathology & Centre for Colorectal Disease, St Vincent's University Hospital & University College, Dublin, Ireland
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University Innsbruck, Innsbruck, Austria
| | | | - Maria Westerhoff
- Department of Pathology, University of Michigan, Ann Arbor, MI, USA
| | - Michael Vieth
- Institute of Pathology, Klinikum Bayreuth GmbH, Preuschwitzer Str. 101, 95445, Bayreuth, Germany.
- Institute of Pathology, Friedrich-Alexander University, Erlangen, Germany.
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24
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Neri B, Mossa M, Scucchi L, Sena G, Palmieri G, Biancone L. Histological scores in inflammatory bowel disease. J Dig Dis 2021; 22:9-22. [PMID: 32897005 DOI: 10.1111/1751-2980.12937] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 09/02/2020] [Accepted: 09/03/2020] [Indexed: 12/11/2022]
Abstract
The role of histology in inflammatory bowel disease (IBD) has not yet been well defined. Endoscopic mucosal healing has been proposed as a predictor of the clinical course of IBD and it is indeed considered one of the main therapeutic targets. However, it does not necessarily imply histological healing. Histological remission has been reported to be associated with a better clinical outcome than endoscopic remission only in IBD patients. These observations support the view that histology plays a role as a potential therapeutic target in Crohn's disease and ulcerative colitis. Histological scores being able to quantify the degree of microscopic activity are needed for this purpose. In the era of biologics, indication for proper treatment may benefit from the assessment of clinical and endoscopic activity, as well as histological scores. Such scores may allow us to quantify the microscopic mucosal response to treatment and to define complete healing in IBD. A validated histological score in IBD may lead to the definition of microscopic activity in clinical practice, trials and investigational settings. Several attempts to develop such scores have been reported, but few are currently used and none is applied worldwide in clinical practice. The present review summarizes the main histological scores currently used for assessing IBD activity.
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Affiliation(s)
- Benedetto Neri
- Department of Systems Medicine, Unit of Gastroenterology, Tor Vergata University, Rome, Italy
| | - Michelangela Mossa
- Department of Systems Medicine, Unit of Gastroenterology, Tor Vergata University, Rome, Italy
| | - Ludovica Scucchi
- Department of Systems Medicine, Unit of Gastroenterology, Tor Vergata University, Rome, Italy
| | - Giorgia Sena
- Department of Systems Medicine, Unit of Gastroenterology, Tor Vergata University, Rome, Italy
| | - Giampiero Palmieri
- Department of Experimental Medicine, Unit of Pathology, Tor Vergata University, Rome, Italy
| | - Livia Biancone
- Department of Systems Medicine, Unit of Gastroenterology, Tor Vergata University, Rome, Italy
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25
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Peverelle M, Paleri S, Hughes J, De Cruz P, Gow PJ. Activity of Inflammatory Bowel Disease After Liver Transplantation for Primary Sclerosing Cholangitis Predicts Poorer Clinical Outcomes. Inflamm Bowel Dis 2020; 26:1901-1908. [PMID: 31944235 DOI: 10.1093/ibd/izz325] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND The impact of inflammatory bowel disease (IBD) activity on long-term outcomes after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is unknown. We examined the impact of post-LT IBD activity on clinically significant outcomes. METHODS One hundred twelve patients undergoing LT for PSC from 2 centers were studied for a median of 7 years. Patients were divided into 3 groups according to their IBD activity after LT: no IBD, mild IBD, and moderate to severe IBD. Patients were classified as having moderate to severe IBD if they met at least 1 of 3 criteria: (i) Mayo 2 or 3 colitis or Simple Endoscopic Score-Crohn's Disease ≥7 on endoscopy; (ii) acute flare of IBD necessitating steroid rescue therapy; or (iii) post-LT colectomy for medically refractory IBD. RESULTS Moderate to severe IBD at any time post-transplant was associated with a higher risk of Clostridium difficile infection (27% vs 8% mild IBD vs 8% no IBD; P = 0.02), colorectal cancer/high-grade dysplasia (21% vs 3% both groups; P = 0.004), post-LT colectomy (33% vs 3% vs 0%) and rPSC (64% vs 18% vs 20%; P < 0.001). Multivariate analysis revealed that moderate to severe IBD increased the risk of both rPSC (relative risk [RR], 8.80; 95% confidence interval [CI], 2.81-27.59; P < 0.001) and colorectal cancer/high-grade dysplasia (RR, 10.45; 95% CI, 3.55-22.74; P < 0.001). CONCLUSIONS Moderate to severe IBD at any time post-LT is associated with a higher risk of rPSC and colorectal neoplasia compared with mild IBD and no IBD. Patients with no IBD and mild IBD have similar post-LT outcomes. Future prospective studies are needed to determine if more intensive treatment of moderate to severe IBD improves long-term outcomes in patients undergoing LT for PSC.
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Affiliation(s)
| | - Sarang Paleri
- Liver Transplant Unit, Heidelberg, Victoria, Australia
| | - Jed Hughes
- Liver Transplant Unit, Heidelberg, Victoria, Australia
| | - Peter De Cruz
- Department of Gastroenterology, Austin Health, Heidelberg, Victoria, Australia.,Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
| | - Paul J Gow
- Liver Transplant Unit, Heidelberg, Victoria, Australia.,Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
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26
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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: 111] [Impact Index Per Article: 22.2] [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.
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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
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27
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Batra SK, Heier CR, Diaz-Calderon L, Tully CB, Fiorillo AA, van den Anker J, Conklin LS. Serum miRNAs Are Pharmacodynamic Biomarkers Associated With Therapeutic Response in Pediatric Inflammatory Bowel Disease. Inflamm Bowel Dis 2020; 26:1597-1606. [PMID: 32793975 PMCID: PMC7500519 DOI: 10.1093/ibd/izaa209] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND We sought to identify microRNAs (miRNAs) associated with response to anti-TNF-α or glucocorticoids in children with inflammatory bowel disease (IBD) to generate candidate pharmacodynamic and monitoring biomarkers. METHODS Clinical response was assessed by Pediatric Crohn's Disease Activity Index and Pediatric Ulcerative Colitis Activity Index. Quantitative real-time polymerase chain reaction via Taqman Low-Density Array cards were used to identify miRNAs in a discovery cohort of responders (n = 11) and nonresponders (n = 8). Seven serum miRNAs associated with clinical response to treatment, along with 4 previously identified (miR-146a, miR-146b, miR-320a, miR-486), were selected for further study. Candidates were assessed in a validation cohort of serum samples from IBD patients pre- and post-treatment and from healthy controls. Expression of miRNA was also analyzed in inflamed mucosal biopsies from IBD patients and non-IBD controls. RESULTS Discovery cohort analysis identified 7 miRNAs associated with therapeutic response: 5 that decreased (miR-126, miR-454, miR-26b, miR-26a, let-7c) and 2 that increased (miR-636, miR-193b). In the validation cohort, 7 of 11 candidate miRNAs changed in the same direction with response to anti-TNF-α therapies, glucocorticoids, or both. In mucosal biopsies, 7 out of 11 miRNAs were significantly increased in IBD vs healthy controls. CONCLUSIONS Five candidate miRNAs associated with clinical response and mucosal inflammation in pediatric IBD patients were identified (miR-126, let-7c, miR-146a, miR-146b, and miR-320a). These miRNAs may be further developed as pharmacodynamic and response monitoring biomarkers for use in clinical care and trials.
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Affiliation(s)
- Suruchi K Batra
- Division of Gastroenterology, Hepatology and Nutrition, Children’s National Hospital, Washington, DC, USA
| | - Christopher R Heier
- Research Center for Genetic Medicine, Children’s National Hospital, Washington, DC, USA,Department of Genomics and Precision Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USA
| | - Lina Diaz-Calderon
- Division of Gastroenterology, Hepatology and Nutrition, Children’s National Hospital, Washington, DC, USA
| | - Christopher B Tully
- Research Center for Genetic Medicine, Children’s National Hospital, Washington, DC, USA
| | - Alyson A Fiorillo
- Research Center for Genetic Medicine, Children’s National Hospital, Washington, DC, USA,Department of Genomics and Precision Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USA
| | - John van den Anker
- Division of Clinical Pharmacology, Children’s National Hospital, Washington, DC, USA
| | - Laurie S Conklin
- Division of Gastroenterology, Hepatology and Nutrition, Children’s National Hospital, Washington, DC, USA,Address correspondence to: Laurie S. Conklin, MD, Children’s National Hospital, 111 Michigan Ave NW, Washington, DC 20010, USA. E-mail:
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28
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Sood A, Singh A, Mahajan R, Midha V, Kaur K, Singh D, Bansal N, Dharni K. Clinical Predictors of response to Faecal Microbiota Transplantation in patients with active ulcerative colitis. J Crohns Colitis 2020; 15:jjaa163. [PMID: 32772093 DOI: 10.1093/ecco-jcc/jjaa163] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Indexed: 01/16/2023]
Abstract
BACKGROUND Fecal Microbiota Transplantation (FMT) has been shown to be effective for induction of remission in patients with active ulcerative colitis (UC). At present, clinical factors impacting the response to FMT in UC remain unclear. METHODS Patients with active UC treated with multisession FMT via colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22, were analysed. Response to FMT was defined as achievement of corticosteroid free clinical remission at week 30. Patient and disease characteristics were evaluated to determine the predictors of response to FMT. RESULTS Out of 140 patients with active UC treated with FMT, 93 patients [mean age 34.96±11.27 years, 62.36% males (n=58), mean Mayo clinic score 8.07±2.00] who completed the multi-session FMT protocol were analysed. Fifty-seven (61.29%) patients achieved clinical remission. Younger age (OR for age 0.93, 95% CI 0.89-0.97, p=0.001), moderate (Mayo clinic score 6-9) disease severity (OR 3.01, 95% CI 1.12 to 8.06, p=0.025) and endoscopic Mayo score 2 (OR 5.55, 95% CI 2.18-14.06, p<0.001) were significant predictors of remission on univariate analysis. Younger age, disease extent E2 and endoscopic mayo score 2 (OR 0.925, 95% CI 0.88-0.97, p=0.002; OR 2.89, 95% CI 1.01-8.25, p=0.04 and OR 8.43, 95% CI 2.38-29.84, p=0.001, respectively) were associated with clinical remission on multivariate logistic regression. A mathematical model (nomogram) was developed for estimating the probability of remission with FMT protocol. CONCLUSION Younger age, disease extent E2, and endoscopic mayo score 2 significantly predict achievement of clinical remission with FMT in active UC. The prediction model can help in selecting individuals for FMT. Validation in larger cohorts is needed.
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Affiliation(s)
- Ajit Sood
- Internal Medicine, DM Gastroenterology, Department of Gastroenterology, Dayanand Medical College, Ludhiana, Punjab, India
| | - Arshdeep Singh
- Internal Medicine, DM Gastroenterology, Department of Gastroenterology, Dayanand Medical College, Ludhiana, Punjab, India
| | - Ramit Mahajan
- Internal Medicine, DM Gastroenterology, Department of Gastroenterology, Dayanand Medical College, Ludhiana, Punjab, India
| | - Vandana Midha
- Internal Medicine, Department of Internal Medicine, Dayanand Medical College, Ludhiana, Punjab, India
| | - Kirandeep Kaur
- Pharmacology, Department of Pharmacology, Dayanand Medical College, Ludhiana, Punjab, India
| | - Dharmatma Singh
- CRC, Research and Development Centre, Dayanand Medical College, Ludhiana, Punjab, India
| | - Namita Bansal
- Statistician, Research and Development Centre, Dayanand Medical College, Ludhiana, Punjab, India
| | - Khushdeep Dharni
- School of Business Studies, Punjab Agricultural University, Ludhiana, Punjab, India
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Lightner AL, Vaidya P, Vogler S, McMichael J, Jia X, Regueiro M, Qazi T, Steele SR, Church J. Surveillance pouchoscopy for dysplasia: Cleveland Clinic Ileoanal Pouch Anastomosis Database. Br J Surg 2020; 107:1826-1831. [PMID: 32687623 DOI: 10.1002/bjs.11811] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 05/01/2020] [Accepted: 05/26/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND No formal guidelines exist for surveillance pouchoscopy following ileal pouch-anal anastomosis (IPAA) for ulcerative colitis. METHODS All adults who had previously had IPAA for ulcerative colitis, and underwent a pouchoscopy between 1 January 2010 and 1 January 2020, were included. RESULTS A total of 9398 pouchoscopy procedures were performed in 3672 patients. The majority of the examinations were diagnostic (8082, 86·0 per cent; 3260 patients) and the remainder were for routine surveillance (1316, 14·0 per cent; 412 patients). Thirteen patients (0·14 per cent of procedures) were found to have biopsy-proven neoplasia at the time of pouchoscopy; seven had low-grade dysplasia (LGD) (0·07 per cent; all located in the anal transition zone), none had high-grade dysplasia (HGD) and six (0·06 per cent) had invasive adenocarcinoma (4 in anal transition zone and 6 in pouch). Of the six patients with adenocarcinoma, four had neoplasia at the time of proctocolectomy (2 adenocarcinoma, 1 LGD, 1 HGD); all six were symptomatic with anal bleeding or pelvic pain at the time of pouchoscopy, had a negative surveillance pouchoscopy examination within 2 years of diagnosis of adenocarcinoma, had palpable masses on digital rectal examination, and had visible lesions at the time of pouchoscopy. CONCLUSION Surveillance pouchoscopy is not recommended in asymptomatic patients because significant neoplasia following IPAA for ulcerative colitis is rare.
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Affiliation(s)
- A L Lightner
- Departments of Colorectal Surgery, Cleveland, Ohio, USA
| | - P Vaidya
- Departments of Colorectal Surgery, Cleveland, Ohio, USA
| | - S Vogler
- Departments of Colorectal Surgery, Cleveland, Ohio, USA
| | | | - X Jia
- Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - M Regueiro
- Gastroenterology, Digestive Disease Surgical Institute, Cleveland, Ohio, USA
| | - T Qazi
- Gastroenterology, Digestive Disease Surgical Institute, Cleveland, Ohio, USA
| | - S R Steele
- Departments of Colorectal Surgery, Cleveland, Ohio, USA
| | - J Church
- Departments of Colorectal Surgery, Cleveland, Ohio, USA
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Langhorst J, Kairey L, Oberle A, Boone J, Dobos G, Juette H, Tannapfel A, Rueffer A. Assessing Histological Inflammatory Activity in Patients With Ulcerative Colitis: A Diagnostic Accuracy Study Testing Fecal Biomarkers Lactoferrin and Calprotectin. CROHN'S & COLITIS 360 2020; 2:otaa053. [PMID: 36776494 PMCID: PMC9802191 DOI: 10.1093/crocol/otaa053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Indexed: 11/13/2022] Open
Abstract
Background and Aims Histological remission has arisen as the optimal treatment outcome in ulcerative colitis (UC). The aim of this retrospective study was to explore the diagnostic performance of the noninvasive fecal biomarkers calprotectin (FC) and lactoferrin (FL) compared to the histological indices Nancy Index (NI) and Riley Index (RI). Methods This study is a retrospective diagnostic accuracy study based on secondary analysis of patient data from 2002 to 2017 extracted from medical registries of our clinics in Essen-Mitte, Germany. Patients with UC underwent a colonoscopy, with biopsies taken from the rectum and the sigmoid scored by 2 experienced pathologists according to NI and RI and provided a stool sample within 7 days pre- or post-colonoscopy. Diagnostic accuracy of recommended cutoffs for FC (>50 μg/g) and FL (≥7.25 μg/g) were tested against our reference standard (NI ≥2) in terms of specificity, sensitivity, positive predictive value, negative predictive value, and accuracy (effectiveness). Results The number of patients with UC recruited was n = 226, aged 45.2 (SD 13.3). Histological indices were highly correlated (r = 0.980, P < 0.001). Fecal biomarkers correlated moderately with NI (FC: r = 0.383, P < 0.001; FL: r = 0.420, P < 0.001) and RI (FC: r = 0.395, P < 0.001; FL: r = 0.424, P < 0.001). Fecal biomarker concentrations were increased in patients with active histological disease (NI ≥2), median [IQR], FC 69.72 [20.07-254.38], FL 18.59 [6.06-44.42], compared to those with inactive disease (NI ≤1), FC 12.35 [3.89 - 32.16], FL 3.14 [0.75-11.05], z = -6.60, P < 0.001. Fecal biomarker concentrations differed significantly across NI grades 0-4 (FC: H4 = 45.2; FL: H4 = 47.5, both P < 0.001). Patients with grade 0 had significantly lower concentrations of fecal biomarkers than those with grade 3 (median; FC 10.94 vs 72.22; FL 2.30 vs 29.10; both P < 0.001) or grade 4 (FC 10.94 vs 67.00; FL 2.30 vs 27.64; both P < 0.001), as well as grade 2 for FC only (10.94 vs 56.22, P = 0.001). Concentrations were also lower in patients with grade 1 compared to those with grade 3 (FC 17.49 vs 72.22; FL 4.24 vs. 29.10; both P ≤ 0.001) or grade 4 (FC 17.49 vs 67.00; FL 4.24 vs 27.64; both P < 0.001).Receiver operating characteristics area under the curve showed moderate diagnostic accuracy for both FC 0.76 (95% confidence interval [CI] 0.70-0.83) and FL 0.73 (95% CI 0.66-0.80). Optimized cutoffs for both FC (≥34.29) and FL (≥5.85 μg/g) had slightly improved accuracy, compared with the manufacturer's cutoffs (FC: 69.9% vs 65.9%; FL: 71.7% vs 69.0%). Conclusions Fecal biomarkers calprotectin and lactoferrin correlate with histological disease activity and differentiate between patients in histological remission from those with evidence of moderate to severe disease activity. Their noninvasiveness, in addition to being inexpensive, supports their use in the clinical monitoring of patients with UC.
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Affiliation(s)
- Jost Langhorst
- Department of Internal and Integrative Medicine, Klinikum Bamberg, Bamberg, Germany,Chair for Integrative Medicine, University of Duisburg, Essen, Germany,Address correspondence to: Jost Langhorst, MD, Buger Str. 80, 96049 Bamberg, Germany ()
| | - Lana Kairey
- Department of Internal and Integrative Medicine, Klinikum Bamberg, Bamberg, Germany
| | - Angela Oberle
- Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany
| | | | - Gustav Dobos
- Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany
| | - Hendrik Juette
- Institute for Pathology, Ruhr University Bochum, Bochum, Germany
| | - Andrea Tannapfel
- Institute for Pathology, Ruhr University Bochum, Bochum, Germany
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Mahmoud R, Shah SC, Torres J, Castaneda D, Glass J, Elman J, Kumar A, Axelrad J, Harpaz N, Ullman T, Colombel JF, Oldenburg B, Itzkowitz SH. Association Between Indefinite Dysplasia and Advanced Neoplasia in Patients With Inflammatory Bowel Diseases Undergoing Surveillance. Clin Gastroenterol Hepatol 2020; 18:1518-1527.e3. [PMID: 31446183 PMCID: PMC7354098 DOI: 10.1016/j.cgh.2019.08.032] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Revised: 07/29/2019] [Accepted: 08/16/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Little is known about the clinical significance of indefinite dysplasia (IND) in patients with inflammatory bowel diseases (IBD) undergoing colonoscopic surveillance for colorectal neoplasia. METHODS We conducted a retrospective cohort analysis of 492 patients with colonic IBD for 8 or more years or concomitant primary sclerosing cholangitis, with no history of advanced colorectal neoplasia (high-grade dysplasia or colorectal cancer) or colectomy, undergoing colorectal neoplasia surveillance at a tertiary IBD referral center from 2001 through 2017. Subjects received consistent histopathologic grading of dysplasia. We collected data on time to development of (advanced) colorectal neoplasia or colectomy using Kaplan Meier methods. We identified factors independently associated with (advanced) colorectal neoplasia with multivariable Cox regression analysis. RESULTS After 2149 person-years of follow-up, 53 patients (10.8%) received a diagnosis of IND without prior or synchronous low-grade dysplasia (LGD). Compared to patients without dysplasia, patients with IND had a significantly higher risk of advanced colorectal neoplasia (adjusted hazard ratio, 6.85; 95% CI, 1.78-26.4) and colorectal neoplasia (adjusted hazard ratio, 3.25; 95% CI, 1.50-7.05), but not colectomy (P = .78). Compared to IND, LGD was associated with a significantly higher risk of advanced colorectal neoplasia (P = .05). Following a diagnosis of no dysplasia, IND only, or LGD, the incidence rates of advanced colorectal neoplasia were 0.4% per patient-year, 3.1% per patient-year, and 8.4% per patient-year, respectively. CONCLUSIONS In a retrospective analysis of patients with IBD undergoing colorectal neoplasia surveillance with consistent histopathologic grading of dysplasia, IND was independently associated with a significant increase in risk of advanced colorectal neoplasia. These findings require validation and if confirmed, a reappraisal of the colorectal neoplasia surveillance guidelines.
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Affiliation(s)
- Remi Mahmoud
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Shailja C. Shah
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Joana Torres
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Division of Gastroenterology, Surgical Department, Hospital Beatriz Ângelo, Loures, Portugal
| | - Daniel Castaneda
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jason Glass
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Department of Internal Medicine, Division of Digestive and Liver Sciences, University of Texas Southwestern, Dallas, TX, USA
| | - Jordan Elman
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Akash Kumar
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jordan Axelrad
- Inflammatory Bowel Disease Center, NYU Langone Health, Division of Gastroenterology NYU School of Medicine, New York, NY, USA
| | - Noam Harpaz
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Thomas Ullman
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Division of Gastroenterology, Montefiore Hospital, New York, NY, USA
| | - Jean-Frédéric Colombel
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Bas Oldenburg
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Steven H. Itzkowitz
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Berg DR, Colombel JF, Ungaro R. The Role of Early Biologic Therapy in Inflammatory Bowel Disease. Inflamm Bowel Dis 2019; 25:1896-1905. [PMID: 30934053 PMCID: PMC7185690 DOI: 10.1093/ibd/izz059] [Citation(s) in RCA: 139] [Impact Index Per Article: 23.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Indexed: 12/11/2022]
Abstract
The goals for treatment of inflammatory bowel diseases (IBDs) are changing from elimination of symptoms toward complete disease control-a process that demands both clinical and endoscopic remission. This new IBD treatment paradigm has been shifting from a conventional "step-up" approach toward a more "top-down" early intervention treatment strategy. Recent studies suggest that the use of biologic agents, specifically those targeting tumor necrosis factor alpha, earlier in the treatment course improves patient outcomes and can prevent progression to irreversible bowel damage. Although the strategy of early intervention has accumulating evidence in Crohn's disease, there is less evidence supporting its impact in ulcerative colitis.
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Affiliation(s)
- Dana Rachel Berg
- Inflammatory Bowel Disease Center, Division of Gastroenterology, NYU Langone Health, New York, New York, USA
| | - Jean-Frederic Colombel
- Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Ryan Ungaro
- Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA,Address correspondence to: Ryan Ungaro, MD, MS, 17 East 102nd Street 5th floor, New York, NY 10029 ()
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Macaluso FS, Cavallaro F, Felice C, Mazza M, Armuzzi A, Gionchetti P, Vecchi M, Orlando A. Risk factors and timing for colectomy in chronically active refractory ulcerative colitis: A systematic review. Dig Liver Dis 2019; 51:613-620. [PMID: 30826279 DOI: 10.1016/j.dld.2019.01.018] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2018] [Revised: 01/20/2019] [Accepted: 01/21/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND In patients with chronic refractory ulcerative colitis (UC) the precise timing for indication to colectomy is unclear. AIMS We performed a systematic review of the literature on the risk factors for colectomy in patients with chronic refractory UC in the biologic era. METHODS PubMed Central/Medline and Embase were systemically searched for records published between January 2000 and December 2017. Current evidence was summarized and filtered by expert opinion. RESULTS 70 studies were included in the qualitative synthesis. Several factors were found to be associated with a higher or reduced risk for colectomy, including variables at baseline - such as progression from proctitis/left-sided to extensive colitis, extensive colitis at diagnosis, high baseline C Reactive Protein or erythrocyte sedimentation rate, male gender, and younger age at diagnosis - previous medical history, and factors arising during therapy with biologics, including the absence of clinical response after induction with infliximab or adalimumab, and the lack of mucosal healing during therapy with anti-TNFs. CONCLUSIONS Two main points may help physicians to decide when the surgical option may be considered in patients with chronic refractory UC: (1) a first risk stratification can be obtained by analyzing factors at baseline and medical history, including the previous exposure to anti-TNFs; (2) during therapy with biologics, the early assessment (after 12-16 weeks of treatment) of clinical and endoscopic response is a strong predictor of the subsequent risk of colectomy.
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Affiliation(s)
| | - Flaminia Cavallaro
- Gastroenterology & Digestive Endoscopy Unit, IRCCS Policlinico San Donato, Milano, Italy
| | - Carla Felice
- IBD Unit, "Presidio Columbus" Foundation Hospital "A. Gemelli IRCCS" - Sacro Cuore Catholic University, Rome
| | - Marta Mazza
- Department of Medical and Surgical Sciences (DIMEC), Policlinico S.Orsola-Malpighi, University of Bologna, Italy
| | - Alessandro Armuzzi
- IBD Unit, "Presidio Columbus" Foundation Hospital "A. Gemelli IRCCS" - Sacro Cuore Catholic University, Rome
| | - Paolo Gionchetti
- Department of Medical and Surgical Sciences (DIMEC), Policlinico S.Orsola-Malpighi, University of Bologna, Italy
| | - Maurizio Vecchi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Organ Transplantation, University of Milan, Italy
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Kanazawa M, Takahashi F, Tominaga K, Abe K, Izawa N, Fukushi K, Nagashima K, Kanamori A, Takenaka K, Sugaya T, Iijima M, Takada A, Imai Y, Hiraishi H, Irisawa A. Relationship between endoscopic mucosal healing and histologic inflammation during remission maintenance phase in ulcerative colitis: a retrospective study. Endosc Int Open 2019; 7:E568-E575. [PMID: 30957007 PMCID: PMC6449158 DOI: 10.1055/a-0869-7619] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Accepted: 02/07/2019] [Indexed: 02/06/2023] Open
Abstract
Background and study aims Recently, histological inflammation has been suggested to be an important predictor of sustained remission or relapse of ulcerative colitis (UC). In this study, we retrospectively compared severity of histological inflammation with endoscopic findings in UC patients with mucosal healing (MH) in the remission maintenance phase, and investigated whether histological healing could be a predictor of sustained remission. Patients and methods This study included 166 patients with MH in the remission maintenance phase. Endoscopic evaluation was based on the Mayo endoscopic subscore (MES), and MH was defined as MES 0 or 1. Severity of histological inflammation was graded according to the Matts classification. Patients with Matts 1 and 2 were included in the histological healing (HH) group, and those with Matts 3, 4, and 5, in the non-histological healing (NHH) group. In patients with MH, incidence of relapse was compared and analyzed according to severity of histological inflammation. Results The remission maintenance rate was significantly higher in the MES 0 group than in the MES 1 group ( P = 0.004). The rate was significantly higher in the HH group than in the NHH group ( P = 0.003). Within the MES 1 group, the rate was significantly higher in the HH subgroup than in the NHH subgroup ( P = 0.030). Conclusions This retrospective study suggests that histological healing can be a predictor of sustained remission in UC patients, and examination of histological inflammation provides useful information for long-term management of UC, particularly in patients with MES 1.
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Affiliation(s)
- Mimari Kanazawa
- Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan
| | - Fumiaki Takahashi
- Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan,Department of Internal Medicine, Japanese Red Cross Ashikaga Hospital, Tochigi, Japan
| | - Keiichi Tominaga
- Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan,Corresponding author Keiichi Tominaga, MD, PhD Department of GastroenterologyDokkyo Medical University880, Kitakobayashi, Mibu, ShimotsugaTochigi 321-0293Japan+81 282 867761
| | - Keiichiro Abe
- Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan
| | - Naoya Izawa
- Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan
| | - Koh Fukushi
- Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan
| | - Kazunori Nagashima
- Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan
| | - Akira Kanamori
- Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan
| | - Kazuhiro Takenaka
- Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan
| | - Takeshi Sugaya
- Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan
| | - Makoto Iijima
- Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan
| | - Atsuko Takada
- Department of Diagnostic Pathology, Dokkyo Medical University, Tochigi, Japan
| | - Yasuo Imai
- Department of Diagnostic Pathology, Dokkyo Medical University, Tochigi, Japan
| | - Hideyuki Hiraishi
- Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan
| | - Atsushi Irisawa
- Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan
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35
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Sturm A, Maaser C, Calabrese E, Annese V, Fiorino G, Kucharzik T, Vavricka SR, Verstockt B, van Rheenen P, Tolan D, Taylor SA, Rimola J, Rieder F, Limdi JK, Laghi A, Krustiņš E, Kotze PG, Kopylov U, Katsanos K, Halligan S, Gordon H, González Lama Y, Ellul P, Eliakim R, Castiglione F, Burisch J, Borralho Nunes P, Bettenworth D, Baumgart DC, Stoker J. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 2: IBD scores and general principles and technical aspects. J Crohns Colitis 2019; 13:273-284. [PMID: 30137278 DOI: 10.1093/ecco-jcc/jjy114] [Citation(s) in RCA: 281] [Impact Index Per Article: 46.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Andreas Sturm
- Department of Gastroenterology, DRK Kliniken Berlin I Westend, Berlin, Germany
| | - Christian Maaser
- Outpatients Department of Gastroenterology, Hospital Lüneburg, Lüneburg, Germany
| | - Emma Calabrese
- Department of Systems Medicine, University of Rome, Tor Vergata, Italy
| | - Vito Annese
- Department of Gastroenterology, Valiant Clinic & American Hospital, Dubai, UAE
| | - Gionata Fiorino
- Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
| | - Torsten Kucharzik
- Department of Internal Medicine and Gastroenterology, Hospital Lüneburg, Lüneburg, Germany
| | | | - Bram Verstockt
- Department of Gastroenterology and Hepatology, University Hospitals Leuven and CHROMETA - Translational Research in Gastrointestinal Disorders, KU Leuven, Belgium
| | - Patrick van Rheenen
- Department of Paediatric Gastroenterology, Hepatology and Nutrition, University Medical Center Groningen, Groningen, The Netherlands
| | - Damian Tolan
- Clinical Radiology, St James's University Hospital, Leeds, UK
| | - Stuart A Taylor
- Centre for Medical Imaging, University College London, London, UK
| | - Jordi Rimola
- Department of Radiology, Hospital Clínic Barcelona, Barcelona, Spain
| | - Florian Rieder
- Department of Gastroenterology, Hepatology & Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Jimmy K Limdi
- Department of Gastroenterology, Pennine Acute Hospitals NHS Trust, Manchester; Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK
| | - Andrea Laghi
- Department of Clinical and Surgical Translational Medicine, Sapienza - University of Rome, Rome, Italy
| | - Eduards Krustiņš
- Department of Gastroenterology, Hepatology and Nutrition, Pauls Stradins Clinical University Hospital, Riga, Latvia
| | - Paulo G Kotze
- Colorectal Surgery Unit, Catholic University of Paraná PUCPR, Curitiba, Brazil
| | - Uri Kopylov
- Department of Gastroenterology, Sheba Medical Center, Sackler School of Medicine, Tel Aviv, Israel
| | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, University and Medical School of Ioannina, Ioannina, Greece
| | - Steve Halligan
- Centre for Medical Imaging, University College London, London, UK
| | - Hannah Gordon
- Section of Gastroenterology & Hepatology, Royal London Hospital, London, UK
| | - Yago González Lama
- Department of Gastroenterology, University Hospital Puerta De Hierro, Majadahonda Madrid, Spain
| | - Pierre Ellul
- Department of Medicine, Mater Dei Hospital, Msida, Malta
| | - Rami Eliakim
- Department of Gastroenterology, Sheba Medical Center, Sackler School of Medicine, Tel Aviv, Israel
| | - Fabiana Castiglione
- Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Naples, Italy
| | - Johan Burisch
- Department of Gastroenterology, North Zealand University Hospital; Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark
| | - Paula Borralho Nunes
- Department of Anatomic Pathology, Hospital Cuf Descobertas; Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Dominik Bettenworth
- Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany
| | - Daniel C Baumgart
- Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
| | - Jaap Stoker
- Department of Radiology and Nuclear Medicine, Academic Medical Center AMC, University of Amsterdam, Amsterdam, The Netherlands
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Trivedi PJ, Kiesslich R, Hodson J, Bhala N, Boulton RA, Cooney R, Gui X, Iqbal T, Li KK, Mumtaz S, Pathmakanthan S, Quraishi MN, Sagar VM, Shah A, Sharma N, Siau K, Smith S, Ward S, Widlak MM, Bisschops R, Ghosh S, Iacucci M. The Paddington International Virtual Chromoendoscopy Score in ulcerative colitis exhibits very good inter-rater agreement after computerized module training: a multicenter study across academic and community practice (with video). Gastrointest Endosc 2018; 88:95-106.e2. [PMID: 29548940 DOI: 10.1016/j.gie.2018.02.044] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2017] [Accepted: 02/28/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Electronic virtual chromoendoscopy (EVC) can demonstrate ongoing disease activity in ulcerative colitis (UC), even when Mayo subscores suggest healing. However, applicability of EVC technology outside the expert setting has yet to be determined. METHODS Fifteen participants across 5 centers reviewed a computerized training module outlining high-definition and EVC (iScan) colonoscopy modes. Interobserver agreement was then tested (Mayo score, Ulcerative Colitis Endoscopic Index of Severity [UCEIS], and the Paddington International Virtual Chromoendoscopy Score [PICaSSO] for UC), using a colonoscopy video library (30 cases reviewed pretraining and 30 post-training). Knowledge sustainability was retested in a second round (42 cases; 9/15 participants), 6 months after training provision. RESULTS Pretraining intraclass correlation coefficients (ICC) were good for the Mayo endoscopic subscore (ICC, .775), UCEIS scoring erosions/ulcers (ICC, .770), and UCEIS overall (ICC, .786) and for mucosal (ICC, .754) and vascular components of PICaSSO (ICC, .622). For the vascular components of UCEIS, agreement was only moderate (ICC, .429) and did not enhance post-training (ICC, .417); conversely, use of PICaSSO improved post-training (mucosal ICC, .848; vascular, .746). Histologic correlation using the New York Mt. Sinai System was strong for both PICaSSO components (Spearman's ρ for mucosal: .925; vascular, .873; P < .001 for both). Moreover, accuracy in specifically discriminating quiescent from mild histologic strata was strongest for PICaSSO (area under the receiver operating characteristic curve [AUROC] for mucosal, .781; vascular, .715) compared with Mayo (AUROC, .708) and UCEIS (AUROC for UCEIS overall, .705; vascular, .562; bleeding, .645; erosions/ulcers, .696). Inter-rater reliability for PICaSSO was sustained by round 2 participants (round 1 and 2 ICC for mucosal, .873 and .869, respectively; vascular, .715 and .783, respectively), together with histologic correlation (ρ mucosal, .934; vascular, .938; P < .001 for both). CONCLUSIONS PICaSSO demonstrates good interobserver agreement across all levels of experience, providing excellent correlation with histology. Given the ability to discriminate subtle endoscopic features, PICaSSO may be applied to refine stratified treatment paradigms for UC patients.
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Affiliation(s)
- Palak J Trivedi
- National Institute of Health Research (NIHR) Birmingham, Biomedical Research Centre (BRC), University of Birmingham, Birmingham, United Kingdom; Liver Unit, University Hospitals Birmingham Queen Elizabeth, Birmingham, United Kingdom; Department of Gastroenterology, University Hospitals Birmingham Queen Elizabeth, Birmingham, United Kingdom; Institute of Translational Medicine, Institute of Immunology and Immunotherapy Birmingham, United kingdom
| | - Ralf Kiesslich
- Department of Medicine, Division of Gastroenterology, HSK Hospital, Wiesbaden, Germany
| | - James Hodson
- Institute of Translational Medicine, Institute of Immunology and Immunotherapy Birmingham, United kingdom
| | - Neeraj Bhala
- Department of Gastroenterology, University Hospitals Birmingham Queen Elizabeth, Birmingham, United Kingdom
| | - Ralph A Boulton
- Department of Gastroenterology, University Hospitals Birmingham Queen Elizabeth, Birmingham, United Kingdom
| | - Rachel Cooney
- Department of Gastroenterology, University Hospitals Birmingham Queen Elizabeth, Birmingham, United Kingdom
| | - Xianyong Gui
- Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, Calgary, Alberta, Canada
| | - Tariq Iqbal
- Department of Gastroenterology, University Hospitals Birmingham Queen Elizabeth, Birmingham, United Kingdom
| | - Ka-Kit Li
- Department of Gastroenterology and Hepatology, Leicester Royal Infirmary, Leicester, United Kingdom
| | - Saqib Mumtaz
- Department of Gastroenterology, Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, United Kingdom
| | - Shri Pathmakanthan
- Department of Gastroenterology, University Hospitals Birmingham Queen Elizabeth, Birmingham, United Kingdom
| | - Mohammed Nabil Quraishi
- Department of Gastroenterology, University Hospitals Birmingham Queen Elizabeth, Birmingham, United Kingdom
| | - Vandana M Sagar
- National Institute of Health Research (NIHR) Birmingham, Biomedical Research Centre (BRC), University of Birmingham, Birmingham, United Kingdom; Liver Unit, University Hospitals Birmingham Queen Elizabeth, Birmingham, United Kingdom
| | - Ashit Shah
- Department of Gastroenterology, Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, United Kingdom
| | - Naveen Sharma
- Department of Gastroenterology, University Hospitals Birmingham Heart of England Foundation Trust, Birmingham, United Kingdom
| | - Keith Siau
- Department of Gastroenterology, Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, United Kingdom
| | - Samuel Smith
- Department of Gastroenterology, University Hospitals Birmingham Queen Elizabeth, Birmingham, United Kingdom
| | - Stephen Ward
- Department of Colorectal Surgery, University Hospitals Coventry and Warwickshire, Coventry, United Kingdom
| | - Monika M Widlak
- Department of Gastroenterology, University Hospitals Coventry and Warwickshire, Coventry, United Kingdom; Warwick Medical School, University of Warwick, Warwick, United Kingdom
| | - Raf Bisschops
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Subrata Ghosh
- National Institute of Health Research (NIHR) Birmingham, Biomedical Research Centre (BRC), University of Birmingham, Birmingham, United Kingdom; Department of Gastroenterology, University Hospitals Birmingham Queen Elizabeth, Birmingham, United Kingdom; Institute of Translational Medicine, Institute of Immunology and Immunotherapy Birmingham, United kingdom; Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada
| | - Marietta Iacucci
- National Institute of Health Research (NIHR) Birmingham, Biomedical Research Centre (BRC), University of Birmingham, Birmingham, United Kingdom; Department of Gastroenterology, University Hospitals Birmingham Queen Elizabeth, Birmingham, United Kingdom; Institute of Translational Medicine, Institute of Immunology and Immunotherapy Birmingham, United kingdom; Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada
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Parragi L, Fournier N, Zeitz J, Scharl M, Greuter T, Schreiner P, Misselwitz B, Safroneeva E, Schoepfer AM, Vavricka SR, Rogler G, Biedermann L. Colectomy Rates in Ulcerative Colitis are Low and Decreasing: 10-year Follow-up Data From the Swiss IBD Cohort Study. J Crohns Colitis 2018; 12:811-818. [PMID: 29617750 DOI: 10.1093/ecco-jcc/jjy040] [Citation(s) in RCA: 81] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Accepted: 03/27/2018] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Previous population-based studies in patients with ulcerative colitis [UC] revealed variable colectomy rates and colectomy-associated risk factors. Over the past two decades, a decrease in colectomy rates was observed. We assessed risk factors and colectomy rates over time in UC in the Swiss Inflammatory Bowel Disease Cohort Study [SIBDCS]. METHODS Prospectively collected SIBDCS data, including disease history, baseline characteristics at enrolment, and course of disease, were retrospectively analysed. Cumulative and adjusted annual colectomy rates were calculated. RESULTS Among 1245 UC patients analysed [54.6% male], 114 [9.2%] underwent colectomy. We observed 5-, 10-, 15-, and 20-year cumulative colectomy rates after diagnosis of 4.1%, 6.4%, 10.4%, and 14.4% of patients, respectively. Male sex (odds ratio [OR] 1.54; p = 0.035), pancolitis at diagnosis [OR = 2.16; p = 0.005], younger age at diagnosis [OR 0.89 per 5 years of age; p = 0.006] and presence of extraintestinal manifestations [EIM] [OR 2.30; p < 0.001] were risk factors for undergoing colectomy. We did not observe a significant protective effect of smoking on colectomy risk [OR 0.64; p = 0.106]. The majority of colectomies were performed within first 10 years of disease onset, with a rapidly decreasing colectomy rate after 15 years. In patients diagnosed after 2003, colectomy was performed much earlier during and individual's disease course. Nevertheless, we found a significantly decreasing trend in yearly colectomy rates over time after 2005. CONCLUSIONS Crude and adjusted colectomy rates in Swiss UC patients were lower than those reported previously in the literature, and decreased over time.
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Affiliation(s)
- Levente Parragi
- Division of Gastroenterology, University Hospital Zurich [USZ] and University of Zurich, Zurich, Switzerland
| | - N Fournier
- Institute of Social and Preventive Medicine [IUMSP], Lausanne University Hospital, Lausanne, Switzerland
| | - Jonas Zeitz
- Division of Gastroenterology, University Hospital Zurich [USZ] and University of Zurich, Zurich, Switzerland
| | - Michael Scharl
- Division of Gastroenterology, University Hospital Zurich [USZ] and University of Zurich, Zurich, Switzerland
| | - Thomas Greuter
- Division of Gastroenterology, University Hospital Zurich [USZ] and University of Zurich, Zurich, Switzerland
| | - Philipp Schreiner
- Division of Gastroenterology, University Hospital Zurich [USZ] and University of Zurich, Zurich, Switzerland
| | - Benjamin Misselwitz
- Division of Gastroenterology, University Hospital Zurich [USZ] and University of Zurich, Zurich, Switzerland
| | - Ekaterina Safroneeva
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
| | - A M Schoepfer
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois [CHUV] and University of Lausanne, Lausanne, Switzerland
| | - Stephan R Vavricka
- Division of Gastroenterology, Triemli Hospital Zurich, Zurich, Switzerland
| | - Gerhard Rogler
- Division of Gastroenterology, University Hospital Zurich [USZ] and University of Zurich, Zurich, Switzerland
| | - Luc Biedermann
- Division of Gastroenterology, University Hospital Zurich [USZ] and University of Zurich, Zurich, Switzerland
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Fernández-Blanco JI, Fernández-Díaz G, Cara C, Vera MI, Olivares D, Taxonera C. Adalimumab for Induction of Histological Remission in Moderately to Severely Active Ulcerative Colitis. Dig Dis Sci 2018; 63:731-737. [PMID: 29372480 DOI: 10.1007/s10620-018-4935-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Accepted: 01/16/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Histological remission represents a target distinct from endoscopic healing in ulcerative colitis (UC) and seems a better predictor of clinical outcomes. AIMS The aim of this study was to assess the ability of adalimumab to achieve histological remission in UC patients. METHODS Single-center, retrospective, open-label study of patients treated with adalimumab. Eligible patients were anti-TNF naïve adults with moderately to severely active UC. The Mayo score including endoscopy was performed at baseline and weeks 8 and 52. Histological activity was scored using the Geboes Index. The primary endpoint was histological remission, defined as a Geboes grade ≤ 3.0, at week 52. RESULTS We included 34 patients. At week 8, 6 of 34 patients (17.6%) achieved histological remission. At week 52, 9 patients (26.5%, intention to treat; 31%, per protocol) had histological remission. Patients had a significant and progressive reduction in the most severe subgrades of Geboes Index from baseline at weeks 8 and 52. At weeks 8 and 52, 50 and 61.8% of patients achieved mucosal healing (Mayo endoscopic subscore 0-1). All patients who achieved histological remission also had mucosal healing. At week 8, 85.3 and 20.6% of patients achieved clinical response (decrease in Mayo score ≤ 3 points) or remission (Mayo score ≤ 2), respectively. At week 52, the corresponding values were 67.6 and 52.9%, respectively. At week 52, agreement between histological remission and mucosal healing was fair (kappa 0.293). Agreement between histological remission and Mayo endoscopic subscore 0 was good (kappa 0.71). CONCLUSIONS Adalimumab was able to achieve histological remission in anti-TNF naïve patients with moderately to severely active UC.
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Affiliation(s)
| | | | - Carlos Cara
- Inflammatory Bowel Disease Unit, Hospital Universitario la Moncloa, Madrid, Spain
| | - María I Vera
- Inflammatory Bowel Disease Unit, Hospital Universitario la Moncloa, Madrid, Spain.,Department of Gastroenterology, Hospital Puerta de Hierro, Madrid, Spain
| | - David Olivares
- Inflammatory Bowel Disease Unit, Department of Gastroenterology, Hospital Clínico San Carlos, Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), C/Profesor Martín Lagos s/n, 28040, Madrid, Spain
| | - Carlos Taxonera
- Inflammatory Bowel Disease Unit, Hospital Universitario la Moncloa, Madrid, Spain. .,Inflammatory Bowel Disease Unit, Department of Gastroenterology, Hospital Clínico San Carlos, Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), C/Profesor Martín Lagos s/n, 28040, Madrid, Spain.
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Iacucci M, Kaplan GG, Panaccione R, Akinola O, Lethebe BC, Lowerison M, Leung Y, Novak KL, Seow CH, Urbanski S, Minoo P, Gui X, Ghosh S. A Randomized Trial Comparing High Definition Colonoscopy Alone With High Definition Dye Spraying and Electronic Virtual Chromoendoscopy for Detection of Colonic Neoplastic Lesions During IBD Surveillance Colonoscopy. Am J Gastroenterol 2018; 113:225-234. [PMID: 29134964 DOI: 10.1038/ajg.2017.417] [Citation(s) in RCA: 105] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Accepted: 09/12/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Dye spraying chromoendoscopy (DCE) is recommended for the detection of colonic neoplastic lesions in inflammatory bowel disease (IBD). The majority of neoplastic lesions are visible endoscopically and therefore targeted biopsies are appropriate for surveillance colonoscopy. To compare three different techniques for surveillance colonoscopy to detect colonic neoplastic lesions in IBD patients: high definition (HD), (DCE), or virtual chromoendoscopy (VCE) using iSCAN image enhanced colonoscopy. METHODS A randomized non-inferiority trial was conducted to determine the detection rates of neoplastic lesions in IBD patients with longstanding colitis. Patients with inactive disease were enrolled into three arms of the study. Endoscopic neoplastic lesions were classified by the Paris classification and Kudo pit pattern, then histologically classified by the Vienna classification. RESULTS A total of 270 patients (55% men; age range 20-77 years, median age 49 years) were assessed by HD (n=90), VCE (n=90), or DCE (n=90). Neoplastic lesion detection rates in the VCE arm was non-inferior to the DCE arm. HD was non-inferior to either DCE or VCE for detection of all neoplastic lesions. In the lesions detected, location at right colon and the Kudo pit pattern were predictive of neoplastic lesions (OR 6.52 (1.98-22.5 and OR 21.50 (8.65-60.10), respectively). CONCLUSIONS In this randomized trial, VCE or HD-WLE is not inferior to dye spraying colonoscopy for detection of colonic neoplastic lesions during surveillance colonoscopy. In fact, in this study HD-WLE alone was sufficient for detection of dysplasia, adenocarcinoma or all neoplastic lesions.
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Affiliation(s)
- Marietta Iacucci
- Inflammatory Bowel Disease Clinic Division of Gastroenterology & Hepatology, Department of Medicine, University of Calgary, Cumming School of Medicine, Calgary, Canada.,Division of Gastroenterology & Institute of Translational Medicine, NIHR Biomedical Research Center, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Gilaad G Kaplan
- Inflammatory Bowel Disease Clinic Division of Gastroenterology & Hepatology, Department of Medicine, University of Calgary, Cumming School of Medicine, Calgary, Canada
| | - Remo Panaccione
- Inflammatory Bowel Disease Clinic Division of Gastroenterology & Hepatology, Department of Medicine, University of Calgary, Cumming School of Medicine, Calgary, Canada
| | - Oluseyi Akinola
- Inflammatory Bowel Disease Clinic Division of Gastroenterology & Hepatology, Department of Medicine, University of Calgary, Cumming School of Medicine, Calgary, Canada
| | - Brendan Cord Lethebe
- Department of Community Health Sciences, Clinical Research Unit, Cumming School of Medicine, University of Calgary, Calgary, Canada
| | - Mark Lowerison
- Department of Community Health Sciences, Clinical Research Unit, Cumming School of Medicine, University of Calgary, Calgary, Canada
| | - Yvette Leung
- Inflammatory Bowel Disease Clinic Division of Gastroenterology & Hepatology, Department of Medicine, University of Calgary, Cumming School of Medicine, Calgary, Canada
| | - Kerri L Novak
- Inflammatory Bowel Disease Clinic Division of Gastroenterology & Hepatology, Department of Medicine, University of Calgary, Cumming School of Medicine, Calgary, Canada
| | - Cynthia H Seow
- Inflammatory Bowel Disease Clinic Division of Gastroenterology & Hepatology, Department of Medicine, University of Calgary, Cumming School of Medicine, Calgary, Canada.,Department of Community Health Sciences, Clinical Research Unit, Cumming School of Medicine, University of Calgary, Calgary, Canada
| | - Stefan Urbanski
- Department of Pathology, University of Calgary, Cumming School of Medicine, Calgary, Canada
| | - Parham Minoo
- Department of Pathology, University of Calgary, Cumming School of Medicine, Calgary, Canada
| | - Xianyong Gui
- Department of Pathology, University of Calgary, Cumming School of Medicine, Calgary, Canada
| | - Subrata Ghosh
- Inflammatory Bowel Disease Clinic Division of Gastroenterology & Hepatology, Department of Medicine, University of Calgary, Cumming School of Medicine, Calgary, Canada.,Division of Gastroenterology & Institute of Translational Medicine, NIHR Biomedical Research Center, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
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Calafat M, Lobatón T, Hernández-Gallego A, Mañosa M, Torres P, Cañete F, Cabré E, Ojanguren I, Domènech E. Acute histological inflammatory activity is associated with clinical relapse in patients with ulcerative colitis in clinical and endoscopic remission. Dig Liver Dis 2017; 49:1327-1331. [PMID: 28958412 DOI: 10.1016/j.dld.2017.08.041] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2017] [Revised: 08/22/2017] [Accepted: 08/27/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND It has been suggested that acute histological activity has a prognostic value in the outcome of ulcerative colitis (UC) patients in clinical and endoscopic remission. Our aim was to assess the role of histology as a risk factor for clinical relapse (CR) in patients in both clinical and endoscopic remission. METHODS Patients with left-sided or extensive UC in clinical and endoscopic remission (Mayo endoscopic subscore ≤1) undergoing colonoscopy for dysplasia surveillance with random colonic biopsies between 2005-2015 were included. Basal plasmacytosis, acute (AHA), and the chronic (CHA) histological inflammatory activity of all biopsy sets were evaluated. RESULTS One hundred and thirteen patients were included. Median time in clinical remission at inclusion was 27 months (IQR 15-56). Eight percent of patients relapsed within the first year and 33% during the whole follow-up period. In the univariate analysis, the presence of AHA, alone (P=0.048) or together with a past flare within the previous 12 months (P=0.01), was associated with CR within the first year of follow-up. In the multivariate analysis, AHA, together with a flare within the previous 12 months, remained the only risk factor for relapse (RR=7.5; IC95%; 1.8-29.9; P=0.005). CONCLUSIONS In UC patients in clinical and endoscopic remission, the presence of AHA is a risk factor for clinical relapse.
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Affiliation(s)
- Margalida Calafat
- Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain
| | - Triana Lobatón
- Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain.
| | - Alba Hernández-Gallego
- Department of Pathology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain
| | - Míriam Mañosa
- Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
| | - Paola Torres
- Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain
| | - Fiorella Cañete
- Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain
| | - Eduard Cabré
- Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
| | - Isabel Ojanguren
- Department of Pathology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain
| | - Eugeni Domènech
- Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
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Iacucci M, Daperno M, Lazarev M, Arsenascu R, Tontini GE, Akinola O, Gui XS, Villanacci V, Goetz M, Lowerison M, Lethebe BC, Vecchi M, Neumann H, Ghosh S, Bisschops R, Kiesslich R. Development and reliability of the new endoscopic virtual chromoendoscopy score: the PICaSSO (Paddington International Virtual ChromoendoScopy ScOre) in ulcerative colitis. Gastrointest Endosc 2017; 86:1118-1127.e5. [PMID: 28322774 DOI: 10.1016/j.gie.2017.03.012] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2016] [Accepted: 03/05/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Endoscopic inflammation and healing are important therapeutic endpoints in ulcerative colitis (UC). We developed and validated a new electronic virtual chromoendoscopy (EVC) score that could reflect the full spectrum of mucosal and vascular changes including mucosal healing in UC. METHODS Eight participants reviewed a 60-minute training module outlining 3 different i-SCAN modes demonstrating the entire spectrum of inflammatory mucosal and vascular changes in UC. Performance characteristics in endoscopic scoring and predicting the histologic inflammation with EVC (i-SCAN) by using 20 video clips before (pre-test) and after (post-test) were evaluated. Exploratory univariate factor analysis was performed on Paddington International Virtual Chromoendoscopy Score (PICaSSO) covariates for mucosal and vascular score separately. Subsequently, a proportional odds logistic regression model for the prediction of histologic scores was analyzed. RESULTS The interobserver agreement for Mayo endoscopic score in the pre-test (κ = .85; 95% CI, .78-.90) and the post-test (κ = .85; 95% CI, .77-.90) evaluation were very good. This was also true for the Ulcerative Colitis Endoscopic Index of Severity in the pre-test and post-test score interobserver agreement (κ = .86; 95% CI, .77-.92; and κ = .84; 95% CI, .75-.91, respectively). The interobserver agreement of the PICaSSO endoscopic score was very good in the pre-test and post-test evaluations (κ = .92; 95% CI, .87-.96; and κ = .89; 95% CI, .84-.94, respectively). The accuracy of the overall PICaSSO in assessing histologic abnormalities and inflammation by Harpaz score was 57% (95% CI, 48%-65%), by Robarts Histological Index 72% (95% CI, 64%-79%), and by the extent, chronicity, activity, plus system (full spectrum of histologic changes) 83% (95% CI, 76%-88%). CONCLUSIONS The EVC score "PICaSSO" showed very good interobserver agreement. The new EVC score may be used to define the endoscopic findings of mucosal and vascular healing in UC and reflected the full spectrum of histologic changes.
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Affiliation(s)
- Marietta Iacucci
- Division of Gastroenterology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Division of Gastroenterology, Biomedical Research Centre and Institute of Translational Medicine, University of Birmingham, Birmingham, United Kingdom
| | - Marco Daperno
- Division of Gastroenterology, University of Torino, Torino, Italy
| | - Mark Lazarev
- Division of Gastroenterology, Johns Hopkins Hospital, Baltimore, Maryland, USA
| | - Razvan Arsenascu
- Division of Gastroenterology, Morristown Medical Center, Atlantic Health System, Morristown, New Jersey, USA
| | - Gian Eugenio Tontini
- Department of Biomedical Sciences for the Health Division of Gastroenterology IRCCS Policlinico San Donato, University of Milan, Milan, Italy
| | - Oluseyi Akinola
- Division of Gastroenterology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Xianyong Sean Gui
- Department of Pathology, University of Calgary, Calgary, Alberta, Canada
| | | | - Martin Goetz
- Division of Gastroenterology, University Klinikum, Tubingen, Germany
| | - Mark Lowerison
- Department of Community Health Sciences, Clinical Research Unit, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Brendan Cord Lethebe
- Department of Community Health Sciences, Clinical Research Unit, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Maurizio Vecchi
- Department of Biomedical Sciences for the Health Division of Gastroenterology IRCCS Policlinico San Donato, University of Milan, Milan, Italy
| | - Helmut Neumann
- Interventional Endoscopy Center, I. Medizinische Klinik und Poliklinik, University Hospital, Mainz, Germany
| | - Subrata Ghosh
- Division of Gastroenterology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Division of Gastroenterology, Biomedical Research Centre and Institute of Translational Medicine, University of Birmingham, Birmingham, United Kingdom
| | - Raf Bisschops
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Ralf Kiesslich
- Division of Gastroenterology, Director of Internal Medicine II, HSK Hospital, Wiesbaden, Germany
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Katsanos KH, Papamichael K, Christodoulou DK, Cheifetz AS. Histological healing beyond endoscopic healing in ulcerative colitis: Shall we target the "ultra-deep" remission? Dig Liver Dis 2017; 49:1332-1333. [PMID: 28964677 DOI: 10.1016/j.dld.2017.08.043] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2017] [Accepted: 08/27/2017] [Indexed: 12/11/2022]
Affiliation(s)
- Konstantinos H Katsanos
- Division of Gastroenterology, University Hospital & Faculty of Medicine, School of Health Sciences, University of Ioannina, Greece.
| | - Konstantinos Papamichael
- Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
| | - Dimitrios K Christodoulou
- Division of Gastroenterology, University Hospital & Faculty of Medicine, School of Health Sciences, University of Ioannina, Greece
| | - Adam S Cheifetz
- Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
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Fluxá D, Simian D, Flores L, Ibáñez P, Lubascher J, Figueroa C, Kronberg U, Pizarro G, Castro M, Piottante A, Vial MT, Quera R. Clinical, endoscopic and histological correlation and measures of association in ulcerative colitis. J Dig Dis 2017; 18:634-641. [PMID: 28949435 DOI: 10.1111/1751-2980.12546] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Revised: 08/30/2017] [Accepted: 09/22/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To determine the correlation between clinical, fecal, endoscopic and histological activity in patients with ulcerative colitis (UC). METHODS A correlational cross-sectional analysis was performed in patients with UC who underwent colonoscopy between February and December 2016. Clinical, endoscopic, fecal and histological activities were determined using the partial Mayo subscore, Mayo endoscopic subscore and modified Mayo endoscopic subscore, fecal calprotectin and Geboes score and the presence of basal plasmacytosis, respectively. Scores were analyzed using Spearman's rank correlation test. To determine the association between scores and some clinical variables and active UC, univariate and multivariate logistic regressions were used. RESULTS Altogether 105 procedures (93 patients) were included. In 64.8% of the procedures, the mucosa was inflamed; however, 14.7% did not show histological inflammation. Endoscopic remission was observed in the other 35.2% of procedures; however, in biopsies 21.6% exhibited histological inflammation. Mayo endoscopic subscore and modified Mayo endoscopic score were well correlated but were only moderately correlated with clinical and histological scores. Furthermore, there was a moderate correlation between Mayo endoscopic score and Geboes score. Conversely, histological scores were poorly correlated with partial Mayo score. In multivariate analysis, Geboes score and basal plasmacytosis were predictive of active disease (OR 3.505, 95% CI 1.544-7.959 and OR 3.240, 95% CI 1.123-9.349, respectively), whereas biological therapy was found to be protective against UC (OR 0.021, 95% CI 0.000-0.641). CONCLUSION Clinical, endoscopic and histological activities were moderately correlated, while Geboes score and basal plasmacytosis were predictive of endoscopically active UC.
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Affiliation(s)
- Daniela Fluxá
- Department of Gastroenterology, Clínica Las Condes, Santiago, Chile
| | - Daniela Simian
- Academic Department Research Unit, Clínica Las Condes, Santiago, Chile
| | - Lilian Flores
- Department of Gastroenterology, Inflammatory Bowel Disease Program, Clínica Las Condes, Santiago, Chile
| | - Patricio Ibáñez
- Department of Gastroenterology, Inflammatory Bowel Disease Program, Clínica Las Condes, Santiago, Chile
| | - Jaime Lubascher
- Department of Gastroenterology, Inflammatory Bowel Disease Program, Clínica Las Condes, Santiago, Chile
| | - Carolina Figueroa
- Department of Gastroenterology, Inflammatory Bowel Disease Program, Clínica Las Condes, Santiago, Chile
| | - Udo Kronberg
- Department of Surgery, Colorectal Surgery Unit, Inflammatory Bowel Disease Program, Clínica Las Condes, Santiago, Chile
| | - Gonzalo Pizarro
- Department of Gastroenterology, Clínica Las Condes, Santiago, Chile.,Department of Gastroenterology, Barros Luco Trudeau Hospital, Santiago, Chile
| | - Magdalena Castro
- Academic Department Research Unit, Epidemiology and Biomedical Statistics, Academic Research Unit, Clínica Las Condes, Santiago, Chile
| | | | - María T Vial
- Department of Pathology, Clínica Las Condes, Santiago, Chile
| | - Rodrigo Quera
- Department of Gastroenterology, Inflammatory Bowel Disease Program, Clínica Las Condes, Santiago, Chile
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Christensen B, Hanauer SB, Erlich J, Kassim O, Gibson PR, Turner JR, Hart J, Rubin DT. Histologic Normalization Occurs in Ulcerative Colitis and Is Associated With Improved Clinical Outcomes. Clin Gastroenterol Hepatol 2017; 15:1557-1564.e1. [PMID: 28238954 PMCID: PMC5618439 DOI: 10.1016/j.cgh.2017.02.016] [Citation(s) in RCA: 153] [Impact Index Per Article: 19.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Revised: 02/02/2017] [Accepted: 02/16/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Mucosal healing, determined by histologic analysis, is a potential therapeutic target for patients with ulcerative colitis (UC). However, the histologic features of tissue normalization, as an outcome of treatment, have not been well described. We examined the prevalence and predictive values of normalization of the colonic mucosa, based on histologic analysis (histologic normalization) in patients with UC, and determined its association with risk of clinical relapse, compared with histologic disease quiescence and endoscopic mucosal healing. METHODS We performed a retrospective study of 646 patients with confirmed UC who underwent colonoscopy at a tertiary medical center from August 2005 through October 2013. We reviewed reports from pathology analyses of random mucosal biopsies from each colon segment, and categorized them into 3 groups based on histology findings: (1) normalization (completely normal mucosa with no features of chronicity present), (2) quiescence (crypt atrophy or branching without signs of active inflammation including erosions, abscesses, or focal neutrophil infiltration), or (3) active disease (epithelial infiltration by neutrophils, crypt abscesses, erosions, or ulceration). Histology findings were compared with clinical and endoscopic findings. We assessed variables associated with histology findings and, in patients in clinical remission (Simple Clinical Colitis Activity Index score ≤2 and subscore of ≤1 for stool frequency or rectal bleeding), predictive values for clinical relapse at follow-up evaluations 6 months later or more were calculated. RESULTS Of the 646 patients included in the study, 60% had endoscopic mucosal healing, 40% had histologic quiescence, and 10% had histologic normalization. The level of agreement between mucosal and histologic activity was moderate (agreement for 68% of samples; κ = 0.50; P < .001). On multivariate analysis, only proctitis associated with histologic normalization (P = .002). Of 310 patients in clinical remission at initial review, 25% had a clinical relapse, after a median time of 16 months (interquartile range, 10-23 months). Histologic normalization was independently associated with increased odds of relapse-free survival compared with histologic quiescence (hazard ratio, 4.31; 95% confidence interval, 1.48-12.46; P = .007) and histologic activity (hazard ratio, 6.69; 95% confidence interval, 2.16-20.62; P = .001); mucosal healing was not associated with increased odds of relapse-free survival compared with no mucosal healing (hazard ratio, 1.02; 95% confidence interval, 0.56-1.85; P = .954). CONCLUSIONS Histologic normalization of colonic mucosa can be used as a clinical endpoint for patients with UC. We associated histologic normalization with increased odds of relapse-free survival compared with endoscopic healing or histologic quiescence. Further studies are needed to determine whether histologic normalization should be a goal of treatment for patients with UC.
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Affiliation(s)
- Britt Christensen
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, Illinois; Department of Gastroenterology, Alfred Hospital and Monash University, Melbourne, Australia; Department of Gastroenterology, The Royal Melbourne Hospital, Melbourne, Australia
| | - Stephen B Hanauer
- Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Jonathan Erlich
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, Illinois
| | - Olufemi Kassim
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, Illinois
| | - Peter R Gibson
- Department of Gastroenterology, Alfred Hospital and Monash University, Melbourne, Australia
| | - Jerrold R Turner
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, Illinois; Department of Pathology, University of Chicago Medicine, Chicago, Illinois
| | - John Hart
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, Illinois; Department of Pathology, University of Chicago Medicine, Chicago, Illinois
| | - David T Rubin
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, Illinois.
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Frieri G, Galletti B, Di Ruscio M, Tittoni R, Capannolo A, Serva D, Latella G, Sollima L, Leocata P, Necozione S, Frieri R, Viscido A. The prognostic value of histology in ulcerative colitis in clinical remission with mesalazine. Therap Adv Gastroenterol 2017; 10:749-759. [PMID: 29051786 PMCID: PMC5638180 DOI: 10.1177/1756283x17722926] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 06/22/2017] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND The aim of the study was to compare the prognostic value of histological and endoscopic activity in patients with ulcerative colitis (UC). METHODS Patients in clinical remission for 1 year under treatment with mesalazine underwent a planned colonoscopy with biopsies. Histological activity was scored using the histological activity index (HAI). Endoscopic activity was scored using the Mayo endoscopic subscore (MES). The clinical course was evaluated measuring relapses needing steroids during a follow up of 3 years. RESULTS A total of 52 patients were enrolled into the study and followed up for 3 years. At baseline 29 patients (55.77%) had no endoscopic lesions, and 17 patients (32.69%) showed no histological alteration. At 3 years of follow up, overall, 26 patients (50%) were still in steroid-free remission. Using univariate logistic regression analysis, both histological (HAI ⩾ 1) and endoscopic activity (MES ⩾ 1) were significantly associated with outcome, showing, respectively, a relapse risk (odds ratio [OR]) 16.4 times higher than histological remission (HAI 0) (96% confidence interval [CI]: 3.2-84.3) and 6.3 times higher with respect to endoscopic remission (MES 0) (96% CI: 1.9-21.3). After multivariate logistic regression analysis, histological activity was the only factor significantly associated with outcome (OR 10.2; 95% CI: 1.7-59.4). CONCLUSIONS Histological activity has the most powerful prognostic value in predicting the need for steroids in patients with UC in stable clinical remission on mesalazine. It could be considered as a target of therapy in UC.
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Affiliation(s)
| | - Brigida Galletti
- Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy
| | - Mirko Di Ruscio
- Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy
| | - Rachele Tittoni
- Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy
| | - Annalisa Capannolo
- Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy
| | - Donatella Serva
- Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy
| | - Giovanni Latella
- Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy
| | - Laura Sollima
- Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy
| | - Pietro Leocata
- Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy
| | - Stefano Necozione
- Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy
| | - Rosamarie Frieri
- School of Statistical Sciences,University of Rome “La Sapienza”, Rome, Italy
| | - Angelo Viscido
- Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy
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Abstract
BACKGROUND Mucosal healing as measured by endoscopic activity is the therapeutic target for ulcerative colitis (UC) and associated with improved outcomes. We investigated the clinical utility of fecal calprotectin (FC) levels to predict depth of remission, including histological remission in patients with UC. METHODS We performed a retrospective chart review of patients with UC who underwent a full colonoscopy and FC measured within 6 weeks before colonoscopy at a tertiary inflammatory bowel disease center. Clinical, endoscopic, and histological disease activity was assessed by Patient Reported Outcomes (PRO2), Mayo endoscopic score (0-3), and Nancy score (0-4), respectively. Outcomes of interest included (1) deep remission (PRO2 remission and Mayo score 0) and (2) deeper remission (deep remission plus Nancy score 0/1). Mann-Whitney U and Kruskal-Wallis tests and area under the curve-receiver operating characteristic curve analysis were used to evaluate accuracy of the predictive values. RESULTS In 68 patients, increasing FC levels were significantly associated with disease extent (P = 0.006), Mayo score (P = 0.001), and Nancy scores (P < 0.001). Patients with Mayo score 0/1 and Nancy score ≤1 (n = 20) had significantly lower FC levels compared with Mayo 0/1 and Nancy ≥ 2 (31 versus 231; P < 0.001). FC level of ≤60 μg/g predicted deep remission (area under the curve = 0.92, sensitivity 86%, and specificity 87%) and deeper remission (area under the curve = 0.91, sensitivity 83%, and specificity 90%). CONCLUSIONS FC levels significantly correlated with endoscopic extent, mucosal healing, and histological activity, and reflect microscopic disease activity even in the face of macroscopic healing. An FC level of ≤60 μg/g robustly predicted depth of remission, suggesting that FC can be used instead of colonoscopy in a treat-to-target paradigm in patients with UC.
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Shi HY, Chan FKL, Chan AWH, Higashimori A, Kyaw M, Ching JYL, Luk AKC, Wong SH, Wu JCY, Sung JJY, Ng SC. Accuracy of Faecal Immunochemical Test to Predict Endoscopic and Histological Healing in Ulcerative Colitis: A Prospective Study Based on Validated Histological Scores. J Crohns Colitis 2017; 11:1071-1077. [PMID: 28881876 DOI: 10.1093/ecco-jcc/jjx088] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Accepted: 07/12/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Endoscopic and histological healing are associated with improved clinical outcomes in ulcerative colitis [UC]. We aimed to investigate the predictive value of faecal immunochemical test [FIT] for endoscopic and histological healing in UC. METHODS We measured quantitative FIT and faecal calprotectin [FC] in 140 consecutive UC patients who underwent colonoscopy. We assessed the diagnostic accuracy of FIT for predicting endoscopic healing using the Mayo endoscopic subscore [MES 0/1] and for histological healing using the Geboes score [< 2.0] and Nancy index [grade ≤ 1]. The predictive abilities of FIT were compared with those of FC. RESULTS FIT had an area under the curve [AUC] of 0.77 (95% confidence interval [CI] 0.67-0.86, p < 0.001) for endoscopic healing, an AUC of 0.77 [95% CI 0.67-0.86, p < 0.001] using the Geboes score, and 0.77 [95% CI 0.66-0.85, p < 0.001] using the Nancy Index for histological healing. The AUC of FIT was comparable to that of FC for endoscopic healing [p = 0.773] and histological healing [p = 0.767-0.960], and was comparable to colonoscopy for histological healing [p = 0.384-0.673]. FIT < 50 ng/ml predicted endoscopic healing with a sensitivity, specificity, and positive predictive value [PPV] of 72%, 68%, and 82%, respectively, and for histological healing with a sensitivity, specificity, and PPV of 73-75%, 67%, and 78-80%, respectively. Combining FIT with FC led to a higher specificity [90%] for histological healing. Over 85% of patients with FIT < 50 ng/ml and FC < 50 μg/g achieved histological healing. CONCLUSIONS FIT is highly sensitive and accurate to predict endoscopic and histological healing in UC. It represents a promising non-invasive tool for monitoring mucosal healing in UC.
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Affiliation(s)
- Hai Yun Shi
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing, China.,Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China
| | - Francis K L Chan
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China
| | - Anthony W H Chan
- Department of Anatomical & Cellular Pathology, Chinese University of Hong Kong, Hong Kong, China
| | - Akira Higashimori
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China
| | - Moe Kyaw
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China
| | - Jessica Y L Ching
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China
| | - Arthur K C Luk
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China
| | - Sunny H Wong
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China
| | - Justin C Y Wu
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China
| | - Joseph J Y Sung
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China
| | - Siew C Ng
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China
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Mosli MH, Parker CE, Nelson SA, Baker KA, MacDonald JK, Zou GY, Feagan BG, Khanna R, Levesque BG, Jairath V. Histologic scoring indices for evaluation of disease activity in ulcerative colitis. Cochrane Database Syst Rev 2017; 5:CD011256. [PMID: 28542712 PMCID: PMC6481362 DOI: 10.1002/14651858.cd011256.pub2] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Disease activity can be determined using clinical, endoscopic or histologic criteria in patients with ulcerative colitis (UC). Persistent disease activity is associated with poor outcomes. Histologic disease activity has been shown to be associated with relapse, colectomy and colorectal cancer. The ability to objectively evaluate microscopic disease activity using histology is important for both clinical practice and clinical trials. However, the operating properties of the currently available histologic indices remain unclear. OBJECTIVES A systematic review was undertaken to identify and evaluate the development and operating characteristics of histologic disease activity indices used to assess disease activity in people with ulcerative colitis. SEARCH METHODS We searched MEDLINE, EMBASE, PubMed, CENTRAL and the Cochrane IBD Review Group Specialized Trials Register from inception to 2 December 2016 for applicable studies. There were no language or document type restrictions. SELECTION CRITERIA Any study design (e.g. randomized controlled trials, cohort studies, case series) that evaluated a histologic index in patients with UC were considered for inclusion. Eligible patients were adults (> 18 years), diagnosed with UC using conventional clinical, radiographic, endoscopic and histologic criteria. DATA COLLECTION AND ANALYSIS Two authors (MHM and CEP) independently reviewed the titles and abstracts of the studies identified from the literature search. A standardized form was used to assess eligibility of trials for inclusion and for data extraction.Two authors (MHM and CEP) independently extracted and recorded data, which included the number of patients enrolled, number of patients per treatment arm, patient characteristics including age and gender distribution, and the name of the histologic index. Outcomes (i.e. intra-rater reliability, inter-rater reliability, internal consistency, content validity, criterion validity, construct validity, responsiveness, and feasibility) were recorded for each trial. MAIN RESULTS In total, 126 reports describing 30 scoring indices were identified through the screening process. Eleven of the 30 scoring indices have undergone some form of index validation. Intra-rater reliability was assessed for eight scoring indices. Inter-rater reliability was evaluated for all 11 of the scoring indices. Three of the indices underwent content validation. Two of the included scoring indices assessed criterion validity. Six of the included scoring indices explored content validity. Two of the included scoring indices were tested for responsiveness. AUTHORS' CONCLUSIONS The Nancy Index and the Robarts Histopathology Index have undergone the most validation in that four operating properties including reliability, content validity, construct validity (hypothesis testing) and criterion validity have been tested. However, none of the currently available histologic scoring indices have been fully validated. In order to determine the optimal endpoint for histologic healing in UC, more research is required. The optimal index would need to be fully validated.
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Affiliation(s)
- Mahmoud H Mosli
- King Abdulaziz UniversityKing Abdulaziz University HospitalJeddahSaudi Arabia
- Robarts Research InstituteRobarts Clinical TrialsP.O. Box 5015100 Perth DriveLondonONCanadaN6A 5K8
| | - Claire E Parker
- Robarts Clinical Trials100 Dundas Street, Suite 200LondonONCanadaN6A 5B6
| | | | - Kenneth A Baker
- Robarts Clinical Trials100 Dundas Street, Suite 200LondonONCanadaN6A 5B6
| | - John K MacDonald
- Robarts Clinical TrialsCochrane IBD Group100 Dundas Street, Suite 200LondonONCanadaN6A 5B6
- University of Western OntarioDepartment of MedicineLondonONCanada
| | - GY Zou
- Robarts Clinical Trials100 Dundas Street, Suite 200LondonONCanadaN6A 5B6
- University of Western OntarioDepartment of Epidemiology and BiostatisticsLondonONCanada
| | - Brian G Feagan
- Robarts Clinical Trials100 Dundas Street, Suite 200LondonONCanadaN6A 5B6
- Robarts Clinical TrialsCochrane IBD Group100 Dundas Street, Suite 200LondonONCanadaN6A 5B6
- University of Western OntarioDepartment of MedicineLondonONCanada
- University of Western OntarioDepartment of Epidemiology and BiostatisticsLondonONCanada
| | - Reena Khanna
- Robarts Clinical Trials100 Dundas Street, Suite 200LondonONCanadaN6A 5B6
- University of Western OntarioDepartment of MedicineLondonONCanada
| | | | - Vipul Jairath
- Robarts Clinical Trials100 Dundas Street, Suite 200LondonONCanadaN6A 5B6
- University of Western OntarioDepartment of MedicineLondonONCanada
- University of Western OntarioDepartment of Epidemiology and BiostatisticsLondonONCanada
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Guirgis M, Wendt E, Wang LM, Walsh A, Burger D, Bryant RV, Kent A, Adamson R, Brain O, Travis SPL, Keshav S. Beyond Histological Remission: Intramucosal Calprotectin as a Potential Predictor of Outcomes in Ulcerative Colitis. J Crohns Colitis 2017; 11:460-467. [PMID: 27856523 DOI: 10.1093/ecco-jcc/jjw174] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2016] [Accepted: 11/09/2016] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Histological remission and low faecal calprotectin are positive prognostic factors in ulcerative colitis [UC]. Intramucosal calprotectin [iMC], which can be readily determined by immunohistochemistry, has not so far been evaluated as a predictor of outcome in UC. We aimed to investigate the relationship between iMC and clinical, endoscopic, and histological measures of remission in UC, and the independent prognostic value of iMC. METHODS Ambulant patients with UC were recruited for a study comparing clinical activity indices. Sigmoidoscopy and biopsy were performed at the index visit. Clinical, endoscopic, and histological activity were scored and iMC semi-quantitatively measured using immunohistochemistry for the S100A8/9 heterodimer on colonic biopsies, scored as the mean number of positive cells in five high-power fields [HPF]. At the end of follow-up [6 years], data on steroid use, hospitalisation, and colectomy ['adverse outcomes'] were collected. RESULTS iMC was determined in 83 patients and 20 controls, and correlated with clinical, endoscopic, and histological activity [r = 0.51, 0.65, 0.53, p > 0.001, respectively]. iMC was lowest (median 2.4, interquartile range [IQR]: 5.2-5, p < 0.001) in patients with concordance between clinical, endoscopic, and histological remission. Median iMC > 5/HPF was associated with adverse outcome (hazard ratio [HR] 3.36, confidence interval [CI] 1.58, 7.15, p < 0.001). Only 53%, 33%, and 25% of patients in histological remission with iMC > 5 cells/HPF avoided an adverse outcome after 1, 3, and 6 years, respectively. CONCLUSIONS iMC was lowest in patients with concordant clinical, endoscopic, and histological remission. Median iMC > 5/HPF was associated with adverse outcomes despite histological remission. Therefore iMC is a potentially useful independent marker of activity.
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Affiliation(s)
- Marianne Guirgis
- Translational Gastroenterology Unit, Oxford University Hospital, Oxford, UK
| | - Emily Wendt
- Translational Gastroenterology Unit, Oxford University Hospital, Oxford, UK
| | - Lai Mun Wang
- Department of Cellular Pathology, Oxford University Hospital, Oxford, UK
| | - Alissa Walsh
- Translational Gastroenterology Unit, Oxford University Hospital, Oxford, UK
| | - Daniel Burger
- Translational Gastroenterology Unit, Oxford University Hospital, Oxford, UK
| | - Robert V Bryant
- Translational Gastroenterology Unit, Oxford University Hospital, Oxford, UK
| | - Alex Kent
- Translational Gastroenterology Unit, Oxford University Hospital, Oxford, UK
| | - Rebecca Adamson
- Translational Gastroenterology Unit, Oxford University Hospital, Oxford, UK
| | - Oliver Brain
- Translational Gastroenterology Unit, Oxford University Hospital, Oxford, UK
| | - Simon P L Travis
- Translational Gastroenterology Unit, Oxford University Hospital, Oxford, UK
| | - Satish Keshav
- Translational Gastroenterology Unit, Oxford University Hospital, Oxford, UK
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Abstract
OPINION STATEMENT Therapeutic management of patients with inflammatory bowel diseases (IBDs) has, for years, been tailored towards monitoring patient clinical presentation as a way to gauge therapeutic management. With the advent of newer biological agents, treatment and management have begun to focus on more objective rather than subjective parameters. These objective parameters include endoscopic targets and focus on the impact of mucosal healing, radiologic and histologic targets, patient reported outcomes, and use of non-invasive biomarkers. However, a recent consensus statement has identified clinical/patient-reported outcome (PRO) remission and endoscopic remission (defined as a Mayo endoscopic subscore of 0-1) as the target for UC with histological remission being an adjunctive goal. For CD, clinical/PRO remission defined as resolution of abdominal pain and diarrhea/altered bowel habit and endoscopic remission, defined as resolution of ulceration at ileocolonoscopy, and resolution of findings of inflammation on cross-sectional imaging in patients who cannot be adequately assessed with ileocolonoscopy were the primary targets. Biomarker remission (normal C-reactive protein (CRP) and calprotectin) was considered as an adjunctive target. This approach requires continuous monitoring and therapeutic adjustments with an aim to achieve the target. This article attempts to review the most updated literature regarding the treat to target approach and thus provides current recommendations and supported evidence.
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