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September 16, 2025, 18:51

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Colorectal Strictures in Ulcerative Colitis To the Editor, I read with great interest the article by Shao et al., titled “Risk Factors and Long-Term Prognosis for Colorectal Strictures in Ulcerative Colitis” (1). The authors have provided valuable insights into the natural history and risk stratification of stricture formation in ulcerative colitis (UC). I would like to offer several comments and pose a few questions for further clarification and discussion. First, Figure 1 in the article clearly illustrates that the risk of stricture formation increases with disease duration in UC. The graph appears to show a near-linear progression, with an estimated annual risk of approximately 1.2% per year post-diagnosis. This finding reinforces the understanding that strictures are a time-dependent complication of UC. Second, stricture formation is generally considered a marker of chronic and progressive disease. Therefore, the increased frequency of certain clinical features—such as anemia and extraintestinal manifestations—among patients with strictures may reflect prolonged disease activity rather than being directly caused by the strictures themselves. Similarly, higher rates of corticosteroid use and steroid resistance could also be secondary to a more advanced disease state. In this context, the reported risk factors (older age, elevated ESR and CRP, prior steroid use) may be better interpreted as indirect indicators of disease chronicity rather than primary etiologic factors. Third, it is not surprising that strictures most commonly occur in the sigmoid colon, given its status as the narrowest anatomical segment of the large intestine. Wall thickening in this region is more likely to result in significant luminal narrowing, potentially predisposing this site to stricture formation. Fourth, the relationship between UC and cigarette smoking remains one of the more intriguing and paradoxical findings in inflammatory bowel disease research (2). While smoking is generally associated with a reduced risk of developing UC, the absence of a significant difference in smoking status between patients with and without strictures in this study is noteworthy (3). Further exploration of this finding may yield important mechanistic insights. Fifth, the higher incidence of bowel obstruction in patients with strictures is expected. However, the increased frequency of toxic megacolon in this group is particularly interesting. This could be explained either by the long-standing disease course or possibly by obstruction-induced colonic distension acting as a trigger for toxic megacolon. In light of these observations, I would like to pose the following questions: 1. Is it feasible to classify colonic strictures in UC patients based on clinical parameters such as disease severity, prognosis, or response to treatment? Would such a classification have therapeutic or prognostic value? 2. Are there notable clinical differences between patients with solitary versus multiple strictures? For instance, do patients with multiple strictures have a longer disease duration or higher risk of complications such as colorectal cancer or toxic megacolon? 3. Among the eight patients in whom strictures resolved during follow-up, what were their clinical characteristics? Was remission attributed to specific therapies, or could patient-related factors (e.g., genetic or immunological profiles) have contributed? Furthermore, was the possibility of pseudo-strictures or diagnostic misclassification considered? I commend the authors for their important contribution to our understanding of this complex and clinically relevant complication of UC and would appreciate any additional insights they may offer in response. Sincerely, Cuneyt Kayaalp MD, Professor, Istanbul Atlas University, Department of General Surgery, Istanbul, Turkiye cuneytkayaalp@gmail.com, +90 533 4757434 Reference 1. Shao YP, Han TT, Lv H, Yang ST, Zhu QL, Li J, Li JN. Risk factors and long-term prognosis for colorectal strictures in ulcerative colitis. World J Gastroenterol. 2025 Sep 7;31(33):109938. doi: 10.3748/wjg.v31.i33.109938. PMID: 40933463; PMCID: PMC12417941. 2. Alperen CC, Soydas B, Serin E, Erbayrak M, Savas NA, Unler GK, Meral CE, Toprak U, Boyacioglu AS, Dagli U. Role of Environmental Risk Factors in the Etiology of Inflammatory Bowel Diseases: A Multicenter Study. Dig Dis Sci. 2024 Aug;69(8):2927-2936. doi: 10.1007/s10620-024-08491-w. Epub 2024 Jun 5. PMID: 38837110. 3. Harmandar F, Çekin AH. Preventive care in inflammatory bowel disease. Turk J Gastroenterol. 2017 Jul;28(4):307-310. doi: 10.5152/tjg.2017.190617. PMID: 28699605.

Replied on September 18, 2025, 02:30

Dear Professor Kayaalp, Thank you for your thoughtful comments on our study examining colorectal strictures in ulcerative colitis (UC). Their observations highlight important clinical and pathophysiological considerations that merit detailed discussion. Your observation about the reported risk factors (older age, elevated ESR and CRP, prior steroid use) potentially representing indirect indicators of disease chronicity rather than primary etiologic factors is well-taken. As we discussed in our paper, factors such as steroid use and anemia likely reflect disease course and severity rather than direct causation. However, I would note that the age factor in our analysis refers specifically to age at diagnosis, not current age. Given emerging evidence suggesting potential correlations between aging and fibrosis development, this warrants further investigation to clarify whether there is a direct relationship between older age at UC onset and subsequent stricture formation. Responses to Your Questions Question 1: Stricture Classification A clinical classification system could indeed have therapeutic value. Based on our findings, parameters such as temporal onset (early vs. late after diagnosis), functional status (passable vs. impassable), and treatment responsiveness might form the basis for such a system, particularly given vedolizumab's protective effect. Question 2: Single versus Multiple Strictures Our data is limited in this regard, with only 16 patients (13.8%) having two strictures and 1 patient (0.9%) having three strictures. We found no significant clinical differences between patients with single versus multiple strictures, likely due to insufficient sample size for meaningful subgroup analysis. Question 3: Patients with Stricture Resolution Among the eight patients demonstrating stricture improvement, we rigorously excluded pseudo-strictures and patients who achieved resolution through surgical or endoscopic intervention. The treatment regimens were: four received steroids combined with biologics, one received steroids and immunosuppressants alone, and two patients were treated with 5-ASA with corticosteroids enemas. Given that the pathogenesis of UC-related strictures remains largely unknown, this improvement may reflect regression of inflammatory components rather than true remodeling of fibrosis. Research on UC strictures remains limited compared to other IBD complications. We are currently conducting prospective observational studies examining the response of UC strictures to different biologic agents, and we anticipate that larger sample sizes will provide more definitive insights into optimal management strategies. Thank you again for your engagement with our work. Your comments highlight important areas for continued research in this understudied aspect of UC. Sincerely, Yupei Shao, MD, PhD Department of Gastroenterology Chinese Academy of Medical Sciences and Peking Union Medical College Hospital Beijing, China