Intestinal Research

Review

IBD

The evolving understanding of histology as an endpoint in ulcerative colitis: Shintaro Akiyama, Yusuke Miyatani, David T. Rubin; Intest Res 2024;22(4):389-396. Published online March 13, 2024; DOI: https://doi.org/10.5217/ir.2023.00120

A therapeutic goal for patients with ulcerative colitis (UC) is deep remission including clinical remission and mucosal healing. Mucosal healing was previously defined by endoscopic appearance, but recent studies demonstrate that histological improvements can minimize the risks of experiencing clinical relapse after achieving endoscopic remission, and there is growing interest in the value and feasibility of histological targets of treatment in inflammatory bowel disease, and specifically UC. In this review article, we identify remaining challenges and discuss an evolving role of histology in the management of UC.

Citations

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Sampling Extension, Chronic Infiltrates, and Eosinophils: Support for the Evaluation of Histological Healing in Inflammatory Bowel Disease with Endoscopic Remission
Gabriella Canavese, Enrico Costantino Falco, Davide Giuseppe Ribaldone
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Claudin-2 simplifies histological assessment of activity/remission of ulcerative colitis in real-life daily practice
Gabrio Bassotti, Rachele Del Sordo, Francesco Lanzarotto, Sara Mino, Chiara Ricci, Vincenzo Villanacci
European Journal of Gastroenterology & Hepatology.2025; 37(4): 409. CrossRef
Role of 5-aminosalicylic acid in ulcerative colitis management in 8 Asian territories: a physician survey
Julajak Limsrivilai, Allen Yu-hung Lai, Silvia T. H. Li, Murdani Abdullah, Raja Affendi Raja Ali, Satimai Aniwan, Hoang Huu Bui, Jen-Wei Chou, Ida Normiha Hilmi, Wee Chian Lim, Jose Sollano, Michelle Mui Hian Teo, Shu-Chen Wei, Wai Keung Leung
Intestinal Research.2025; 23(2): 117. CrossRef
Beyond mucosal healing: fecal calprotectin and the path toward histologic remission in ulcerative colitis
Yehyun Park
Intestinal Research.2025; 23(2): 115. CrossRef
Sishen pill alleviates ulcerative colitis via the NLRP3/ASC/Caspase-1 signaling pathway: Comprehensive validation through UPLC-Q-TOF/MS, network pharmacology, molecular docking, and in vivo experiments
Qian Luo, Hongping Long, Chun Guo, Xingxu Wei, Xinyu Wang, Haiyue Zhang, Shuangyang Luo, Zilong Liu, Jiemin Liu, Sainan Zhou, Xiaoyuan Lin
Journal of Chromatography B.2025; 1264: 124735. CrossRef
Optimizing Janus kinase inhibitor therapy for ulcerative colitis: a real-world perspective
Shintaro Akiyama
Intestinal Research.2025;[Epub] CrossRef
Patients with ulcerative colitis who have normalized histology are clinically stable after de-escalation of therapy
Shintaro Akiyama, Joëlle St-Pierre, Cindy Traboulsi, Alexa Silfen, Victoria Rai, Tina G. Rodriguez, Amarachi I. Erondu, Joshua M. Steinberg, Seth R. Shaffer, Britt Christensen, David T. Rubin
npj Gut and Liver.2024;[Epub] CrossRef

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Original Articles

IBD

Vedolizumab for perianal fistulizing Crohn’s disease: systematic review and meta-analysis: Fares Ayoub, Matthew Odenwald, Dejan Micic, Sushila R. Dalal, Joel Pekow, Russell D. Cohen, David T. Rubin, Atsushi Sakuraba; Intest Res 2022;20(2):240-250. Published online February 8, 2022; DOI: https://doi.org/10.5217/ir.2021.00091

Abstract PDF Supplementary Material PubReader ePub

Background/Aims
Perianal fistulas are a debilitating manifestation of Crohn’s disease (CD). Despite the advent of anti-tumor necrosis factor (anti-TNF) therapy, the medical management of fistulizing CD continues to be challenged by unmet needs. We conducted a systematic review and meta-analysis of the effectiveness of vedolizumab for the management of perianal fistulizing CD.
Methods
A search of PubMed, EMBASE and the Cochrane Library was performed from inception to June 2020 for studies reporting rates of perianal fistula healing in CD patients treated with vedolizumab. The primary outcome of interest was complete healing of perianal fistulas and the secondary outcome was partial healing. The pooled fistula healing rates with 95% confidence intervals (CI) were calculated utilizing a random effects model.
Results
A total of 74 studies were initially identified, 4 of which met the inclusion criteria. A total of 198 patients with active perianal fistulas were included, 87% of whom had failed previous anti-TNF therapy. The pooled complete healing rate was 27.6% (95% CI, 18.9%–37.3%) with moderate heterogeneity (I2=49.4%) and the pooled partial healing rate was 34.9% (95% CI, 23.2%–47.7%) with high heterogeneity (I2=67.1%).
Conclusions
In a meta-analysis of 4 studies that included 198 patients with perianal fistulizing CD, the majority of whom had failed previous anti-TNF therapy, vedolizumab treatment led to healing of perianal fistulas in nearly one-third of the patients. The lack of high-quality data and significant study heterogeneity underscores the need for future prospective studies of fistula healing in patients receiving anti-integrin therapy.

Citations

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Kimia Basiji, Nesa Kazemifard, Maryam Farmani, Kasra Jahankhani, Shaghayegh Baradaran Ghavami, Amir Fallahnia, Hesameddin Eghlimi, Adil Mir
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Perianal Crohn's disease: the experience of taking a multiprofessional approach in a tertiary centre setting
Eathar Shakweh, Johncy Baby, Lisa Younge, Phil Tozer, Ailsa Hart
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ACG Clinical Guideline: Management of Crohn's Disease in Adults
Gary R. Lichtenstein, Edward V. Loftus, Anita Afzali, Millie D. Long, Edward L. Barnes, Kim L. Isaacs, Christina Y. Ha
American Journal of Gastroenterology.2025; 120(6): 1225. CrossRef
Perianal Crohn's disease: Current perspectives and a tertiary centre experience
Eathar Shakweh, Johncy Baby, Lisa Younge, Phil Tozer, Ailsa Hart
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Monjur Ahmed, Aniruddha Pratap Singh
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Saudi Journal of Gastroenterology.2025;[Epub] CrossRef
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Arshdeep Singh, Vandana Midha, Gursimran Singh Kochhar, Bo Shen, Ajit Sood
Inflammatory Bowel Diseases.2024; 30(9): 1579. CrossRef
Choosing Therapy for Moderate to Severe Crohn’s Disease
Malcolm Irani, Bincy Abraham
Journal of the Canadian Association of Gastroenterology.2024; 7(1): 1. CrossRef
Perianal fistulizing Crohn’s disease: Current perspectives on diagnosis, monitoring and management with a focus on emerging therapies
Jalpa Devi, David H. Ballard, Tina Aswani-Omprakash, Alyssa M. Parian, Parakkal Deepak
Indian Journal of Gastroenterology.2024; 43(1): 48. CrossRef
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Antonio Tursi, Giammarco Mocci, Angelo Del Gaudio, Alfredo Papa
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Manish Manrai, Atul Abhishek Jha, Saurabh Dawra, Aditya Vikram Pachisia
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The potential for medical therapies to address fistulizing Crohn’s disease: a state-of-the-art review
Mohammad Shehab, Davide De Marco, Peter L. Lakatos, Talat Bessissow
Expert Opinion on Biological Therapy.2024; 24(8): 733. CrossRef
A Crohn-betegég terápiás stratégiája
Klaudia Farkas, Hajnal Székely, Péter Bacsur, Balázs Bánky, Zsuzsa Bianka Élthes, László Harsányi, Katalin Edit Müllner, Ágnes Milassin, Károly Palatka, Patrícia Sarlós, Tamás Szamosi, Tamás Molnár, Pál Miheller
Orvosi Hetilap.2024; 165(Supplement): 1. CrossRef
Terápiás kihívások nehezen kezelhető, penetráló Crohn-betegségben – multidiszciplináris megoldás
Bernadett Farkas, Péter Bacsur, Emese Ivány, Anita Bálint, Mariann Rutka, Klaudia Farkas, Tamás Molnár
Orvosi Hetilap.2024; 165(32): 1252. CrossRef
Refractory Crohn’s Disease: Perspectives, Unmet Needs and Innovations
Luisa Bertin, Martina Crepaldi, Miriana Zanconato, Greta Lorenzon, Daria Maniero, Caterina De Barba, Erica Bonazzi, Sonia Facchin, Marco Scarpa, Cesare Ruffolo, Imerio Angriman, Andrea Buda, Fabiana Zingone, Edoardo Vincenzo Savarino, Brigida Barberio
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Gustavo Drügg Hahn, Petra Anna Golovics, Panu Wetwittayakhlang, Alex Al Khoury, Talat Bessissow, Peter Laszlo Lakatos
Biomedicines.2022; 10(4): 749. CrossRef
The Optimal Management of Fistulizing Crohn’s Disease: Evidence beyond Randomized Clinical Trials
Panu Wetwittayakhlang, Alex Al Khoury, Gustavo Drügg Hahn, Peter Laszlo Lakatos
Journal of Clinical Medicine.2022; 11(11): 3045. CrossRef
Management of Non-response and Loss of Response to Anti-tumor Necrosis Factor Therapy in Inflammatory Bowel Disease
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The Korean Journal of Internal Medicine.2022; 37(5): 906. CrossRef

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IBD

Factors associated with anti-tumor necrosis factor effectiveness to prevent postoperative recurrence in Crohn’s disease: Anthony Buisson, Lisa Cannon, Konstantin Umanskiy, Roger D. Hurst, Neil H. Hyman, Atsushi Sakuraba, Joel Pekow, Sushila Dalal, Russell D. Cohen, Bruno Pereira, David T. Rubin; Intest Res 2022;20(3):303-312. Published online August 4, 2021; DOI: https://doi.org/10.5217/ir.2021.00018

Abstract PDF Supplementary Material PubReader ePub

Background/Aims
We assessed the effectiveness of anti-TNF agents and its associated factors to prevent endoscopic and clinical postoperative recurrence (POR) in Crohn’s disease (CD).
Methods
From a prospectively-maintained database, we retrieved 316 CD patients who underwent intestinal resection (2011–2017). Endoscopic (Rutgeerts index ≥ i2 at 6 months) and clinical (recurrence of symptoms leading to hospitalization or therapeutic escalation) POR were assessed.
Results
In 117 anti-TNF-naïve patients, anti-TNF therapy was more effective than immunosuppressive agents (odds ratio [OR], 8.8; 95% confidence interval [CI], 1.8–43.9; P= 0.008) and no medication/5-aminosalicylates (OR, 5.2; 95% CI, 1.0–27.9; P= 0.05) to prevent endoscopic POR. In 199 patients exposed to anti-TNF prior to the surgery, combination with anti-TNF and immunosuppressive agents was more effective than anti-TNF monotherapy (OR, 2.32; 95% CI, 1.02–5.31; P= 0.046) to prevent endoscopic POR. Primary failure to anti-TNF agent prior to surgery was predictive of anti-TNF failure to prevent endoscopic POR (OR, 2.41; 95% CI, 1.10–5.32; P= 0.03). When endoscopic POR despite anti-TNF prophylactic medication (n = 55), optimizing anti-TNF and adding an immunosuppressive drug was the most effective option to prevent clinical POR (hazard ratio, 7.38; 95% CI, 1.54–35.30; P= 0.012). Anti-TNF therapy was the best option to prevent clinical POR (hazard ratio, 3.10; 95% CI, 1.09–8.83; P= 0.034) in patients with endoscopic POR who did not receive any biologic to prevent endoscopic POR (n = 55).
Conclusions
Anti-TNF was the most effective medication to prevent endoscopic and clinical POR. Combination with anti-TNF and immunosuppressive agents should be considered in patients previously exposed to anti-TNF.

Citations

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Marianne Hupé, Bruno Pereira, Anthony Buisson
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Chak Lam Ip, Ray Boyapati, Rahul Kalla
Current Opinion in Gastroenterology.2024; 40(3): 209. CrossRef
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539 Download
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Review

IBD

Pouchitis in inflammatory bowel disease: a review of diagnosis, prognosis, and treatment: Shintaro Akiyama, Victoria Rai, David T. Rubin; Intest Res 2021;19(1):1-11. Published online November 5, 2020; DOI: https://doi.org/10.5217/ir.2020.00047

Abstract PDF PubReader ePub

Patients with inflammatory bowel disease (IBD) occasionally need a restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) because of medically refractory colitis or dysplasia/cancer. However, pouchitis may develop in up to 70% of patients after this procedure and significantly impair quality of life, more so if the inflammation becomes a chronic condition. About 10% of patients with IBD who develop pouchitis require pouch excision, and several risk factors of the failure have been reported. A phenotype that has features similar to Crohn’s disease may develop in a subset of ulcerative colitis patients following proctocolectomy with IPAA and is the most frequent reason for pouch failure. In this review, we discuss the diagnosis and prognosis of pouchitis, risk factors for pouchitis development, and treatment options for pouchitis, including the newer biological agents.

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Time to Revisit Disease Classification in Inflammatory Bowel Disease: Is the Current Classification of Inflammatory Bowel Disease Good Enough for Optimal Clinical Management?
Bram Verstockt, Brian Bressler, Helena Martinez-Lozano, Dermot McGovern, Mark S. Silverberg
Gastroenterology.2022; 162(5): 1370. CrossRef
Histopathology of Colectomy Specimens Predicts Endoscopic Pouch Phenotype in Patients with Ulcerative Colitis
Shintaro Akiyama, Jacob E. Ollech, Cindy Traboulsi, Victoria Rai, Laura R. Glick, Yangtian Yi, Joseph Runde, Andrea D. Olivas, Christopher R. Weber, Russell D. Cohen, Kinga B. Skowron Olortegui, Roger D. Hurst, Konstantin Umanskiy, Benjamin D. Shogan, Mic
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Network meta-analysis: efficacy of treatment for acute, chronic, and prevention of pouchitis in ulcerative colitis
Stephanie Poo, Danujan Sriranganathan, Jonathan P Segal
European Journal of Gastroenterology & Hepatology.2022; 34(5): 518. CrossRef
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Emmeline Nugent, James M. Church
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Shintaro Akiyama, Emma C. Dyer, David T. Rubin
Diseases of the Colon & Rectum.2022; 65(S1): S77. CrossRef
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Sabrina L. Chen, Adam S. Faye, Shannon Chang
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Dong-Hoon Yang
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504 Download
38 Web of Science
40 Crossref

Case Report

IBD

Enteric infections complicating ulcerative colitis: Dejan Micic, Ayal Hirsch, Namrata Setia, David T. Rubin; Intest Res 2018;16(3):489-493. Published online July 27, 2018; DOI: https://doi.org/10.5217/ir.2018.16.3.489

Abstract PDF PubReader ePub

Enteric infections have previously been postulated to play a role in the pathogenesis of inflammatory bowel disease (IBD), however, little evidence exists in the etiologic role of specific enteric infections in the development of IBD. When encountered in the setting of IBD, enteric infections pose a clinical challenge in management given the competing treatment strategies for infectious conditions and autoimmune disorders. Here we present the case of a young male with enteric infections complicating a new diagnosis of IBD. Our patient's initial clinical presentation included diagnoses of Klebsiella oxytoca isolation and Clostridium difficile infection. Directed therapies to include withdrawal of antibiotics and fecal microbiota transplantation were performed without resolution of clinical symptoms. Given persistence of symptoms and active colitis, the patient was diagnosed with ulcerative colitis (UC), requiring treatments directed at severe UC to include cyclosporine therapy. The finding of multiple enteric infections in a newly presenting patient with IBD is an unexpected finding that has treatment implications.

Citations

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Fan-Hao Wei, Wen-Yin Xie, Pei-Sen Zhao, Wei Gao, Fei Gao
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Inflammatory bowel disease complicated with rare pathogen infection
Jia-Heng Fang, Guo-Xiong Li
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Seo Hyun Kim, You Sun Kim, Seung Hyuk Kim, Won Eui Yoon, Hee Jun Myung, Jeong Seop Moon, Dong Hee Whang
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Animal unit hygienic conditions influence mouse intestinal microbiota and contribute to T-cell-mediated colitis
Mariana Cázares-Olivera, Dominika Miroszewska, Lili Hu, Jacek Kowalski, Ulla-Marjut Jaakkola, Seppo Salminen, Bin Li, Emrah Yatkin, Zhi Chen
Experimental Biology and Medicine.2022; 247(19): 1752. CrossRef
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Zhongmei Sun, Wenjing Pei, Yi Guo, Zhibin Wang, Rui Shi, Xiaowei Chen, Xingjie Zhao, Chen Chen, Jiali Liu, Xiang Tan, Wenjing Yuan, Tangyou Mao
Evidence-Based Complementary and Alternative Medicine.2019; 2019: 1. CrossRef
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Shu-Ling Wang, Bo-Zong Shao, Sheng-Bing Zhao, Xin Chang, Pei Wang, Chao-Yu Miao, Zhao-Shen Li, Yu Bai
Cell Death & Disease.2019;[Epub] CrossRef

9,026 View
102 Download
5 Web of Science
6 Crossref

Systematic Review

Histological inflammation increases the risk of colorectal neoplasia in ulcerative colitis: a systematic review: Ruben J. Colman, David T. Rubin; Intest Res 2016;14(3):202-210. Published online June 27, 2016; DOI: https://doi.org/10.5217/ir.2016.14.3.202

Abstract PDF PubReader ePub

<b>Background/Aims</b><br/>

Ulcerative colitis (UC) patients are at greater risk for the development of colorectal neoplasia. Several individual studies have demonstrated associations between severity of histologic inflammation and colorectal neoplasia. However, a comprehensive systematic review has not been completed. We performed a systematic review and meta-analysis to explore the relationship between histologic inflammation and risk for neoplasia among available observational studies.

Methods

Three databases (EMBASE, MEDLINE and the Cochrane Library) were systematically searched. Studies were included if they included UC patients who underwent colonoscopic assessment and when histologic inflammation and colorectal neoplasia were both reported. Colorectal neoplasia rates were compared. Quantitative meta-analysis was attempted.

Results

Four of 1,422 records found were eligible. Results from 2 case-control studies reported a 3.5-fold increased risk for colorectal neoplasia associated with a single point increase in histologic inflammation. This result was further corroborated by one cohort study that demonstrated increased hazard ratios. The second cohort study reported outcomes for patients with normal gross endoscopy, but had increased histological inflammation when neoplasia was assessed. Finally, this study reported increased risk for neoplastic progression by histological inflammation among patients who were normal by gross endoscopic evaluation. Quantitative meta-analysis was unsuccessful due to heterogeneity between study measures.

Conclusions

There is strong evidence that histologic inflammation among patients with UC increases the risk of colorectal neoplasia. The depth and nature of assessment of additional clinical variables was varied and may have resulted in greater outcome discrepancy. Additional study related to mechanisms of inflammation-related neoplasia and therapeutic modification is needed.

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