Successful treatment of ileocolonic anastomotic stricture with ustekinumab in Crohn’s disease: a case report

Introduction

Ileocolonic resection (ICR) with anastomosis (ICA) is the most commonly performed surgical procedure for the treatment of medically or endoscopically refractory Crohn’s disease (CD). Postoperative ulcers and strictures can develop at ICA and might be due to a combination of post-surgical fibrosis as well as Crohn’s inflammation. ICA strictures are generally considered to result from surgical ischemia rather than active CD and the role of medical therapy for anastomotic stricture is unknown. On the other hand, when inflammation at the ICA is noted, this largely results from underlying CD rather than surgery-associated ischemia. The ICA stricture has been listed as a Rutgeert’s score i4 lesion (1). We present this case in accordance with the CARE reporting checklist (available at https://ales.amegroups.com/article/view/10.21037/ales-23-41/rc).

Case presentation

A 78-year-old woman with CD was referred to our Inflammatory Bowel Disease Center for the management of an anastomotic stricture at the hepatic flexure. She had a past medical history of pulmonary tuberculosis, which had been effectively treated, and stricturing CD, diagnosed in 2006. She had not undergone any prior surgeries or did not have a had history of abscesses and fistulas relating to CD. At the time of her referral, she had a colonoscopy that showed a tight stricture at the hepatic flexure not traversable to a pediatric colonoscope. Repeat surveillance and therapeutic colonoscopy confirmed a tight pinhole fibrotic stricture at the hepatic flexure, which was again not traversable with the pediatric colonoscope. Endoscopic balloon dilation with a 14-mm through-the-scope balloon resulted in colonic perforation needing an urgent subtotal colectomy with an ileosigmoid anastomosis and a defunctioning loop ileostomy. Before the stoma closure 3 months later, a colonoscopy and ileoscopy showed a patent ileocolonic anastomosis at 15 centimeters via the anus and a normal neoterminal ileum via stoma. At this time, the patient was on ciprofloxacin and no other medications for CD. The stoma closure procedure was uneventful but approximately 7 months after surgery, the patient developed symptoms of partial small bowel obstruction including bloating, nausea, alternating constipation, and diarrhea and was started on mesalamine.

A repeat colonoscopy was performed a year after her stoma closure for continued symptoms, which had now worsened, and showed a nearly completely occluded lumen at the level of the ileosigmoid anastomosis due to a combination of a sealed mixed inflammatory and fibrotic stricture at ileosigmoid anastomosis, which was not traversable even with a 5.4-mm endoscope (Figure 1). Endoscopic balloon dilation was attempted but was unsuccessful; gastrografin enema also showed the sealed stricture (Figure 2). Potential surgical options could be resection of the ileosigmoidal anastomosis and ileorectal anastomosis or permanent stoma. The former approach was considered not feasible due to patient’s narrowed pelvis, extensive mesentery artery disease, and high risk of recurrent stricture of re-anastomosis. End ileostomy is also not feasible due to the fact the patient had had a complicated course of diverting ileostomy following the last ICR, including surgical site infection, surgical leaks, abscess, and hematoma. Histology of biopsies from the narrowing showed mild to moderately active chronic inflammation (Figure 3). Additionally, biologic therapy was the only remaining option in the medical treatment of this stricture to prevent. This left a trial of medical therapy an only initial option given that the stricture at the anastomosis was due to a combination of fibrosis and inflammation. Based on her weight, this biologics-naïve patient was treated with of intravenous ustekinumab 390 milligrams as a loading dose. Due to the patient’s history of pulmonary tuberculosis, anti-TNF agents avoided. Additionally, it was felt that ustekinumab may be more effective than gut-specific vedolizumab in stricturing and penetrating diseased patients with CD (Table 1 details pros and cons of the two drugs). Repeat colonoscopy 2 weeks later showed much improved, more patent anastomotic stricture with evidence of mucosal healing along the anastomosis (Figure 4). The anastomotic stricture was approximately 2-cm long. The opened-up anastomotic stricture allowed for the passage of a soft-tip guidewire and endoscopic strictureplasty consisting of stricturotomy with an insulated-tip knife (Figure 5) and placement of endoclips as spacers. Two months later, a repeat colonoscopy with a gastroscope passed through the treated stricture without resistance, and the previously placed clip was still in place (Figure 6). The patient’s symptoms gradually resolved due to the medical and endoscopic treatment. Before starting ustekinumab, the patient had an erythrocyte sedimentation rate (ESR) of 70 mm/hour. However, 5 months after starting ustekinumab treatment, her ESR was 15 mm/hour. She gained back weight and was kept on a maintenance dose (90 mg subcutaneous, every 8 weeks) of ustekinumab. While the patient still occasionally developed obstruction symptoms from the ICA stricture, she was able to be treated with gradual endoscopic stricturotomy. While the patient’s last clinical follow up was in October 2023, her last flexible sigmoidoscopy in March 2023 showed a patent ileosigmoid anastomosis without further endoscopic therapy and a few erosions in the neoterminal ileum.

Figure 1 Nearly completely sealed ileosigmoid anastomosis.

Figure 2 Gastrografin enema image of anastomotic stricture in Crohn’s disease patient. The arrow represents the location of the sealed stricture. L, left.

Figure 3 Side-by-side images of histology of obstructed anastomosis showing ileum with mild to moderately active inflammation using hematoxylin and eosin stain. The left side is 40× magnification and the right side is 100× magnification.

Figure 4 The opening up of the stricture using ustekinumab.

Figure 5 Endoscopic strictureplasty of the stricture.

Figure 6 Patent ileosigmoid anastomosis stricture 2 months following dilation.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent for publication of this case report and accompanying images was waived according to New York Presbyterian ethics committee/IRB-approved Inflammatory Bowel Disease registry.

Discussion

The common non-surgical management of CD-related strictures includes endoscopic balloon dilation, endoscopic stricturotomy, and endoscopic strictureplasty (2). The therapeutic role of use of biological agents in treating CD-related strictures is controversial; prior literature reports the use of biologic agents along with endoscopic balloon dilation in treating CD-associated gastrointestinal strictures (3). There has been a previous reported case of successful treatment of a non-obstructing primary stricture using both ustekinumab and vedolizumab (4). Recently, additionally, a study on adalimumab therapy on CD related strictures showed that responders to the biologic agent at 12 months had a less likelihood of surgery than those who did not respond (5).

Conclusions

This was a mixed inflammatory/fibrotic anastomotic stricture in a patient with underlying CD, and it has been challenging to distinguish the relative contribution of CD-related or surgical ischemia-related factors. There is no current literature on the response of anastomotic stricture to medical therapy; the favorable response to the biological therapy in our case suggests that a component of stricture resulted from of inflammation from underlying CD.

The role of medical therapy for anastomotic strictures in CD is not clear. Our case demonstrated the efficacy of ustekinumab in the treatment of anastomotic stricture in CD and provision of room for concurrent or subsequent endoscopic therapy. Our case illustrates that nearly completely occluded strictures at the anastomosis due to the combination of fibrosis and inflammation may also open with the use of ustekinumab, which then allows endoscopic therapy. The mechanism of action is unclear; however, it is possible that CD-associated inflammation contributed to the severity of the occlusion of the anastomotic stricture. Thus, in this scenario, biological therapy along with endoscopic therapy may be an option for anastomotic strictures in CD.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://ales.amegroups.com/article/view/10.21037/ales-23-41/rc

Peer Review File: Available at https://ales.amegroups.com/article/view/10.21037/ales-23-41/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://ales.amegroups.com/article/view/10.21037/ales-23-41/coif). The authors have no conflicts of interest to disclose.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent for publication of this case report and accompanying images was waived according to New York Presbyterian ethics committee/IRB-approved Inflammatory Bowel Disease registry.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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