Insufficiency of ileocolic anastomosis in Crohn’s disease patients – prevention and treatment

Abstract

Resection of the terminal ileum and ileocecal valve remains the most commonly performed procedure in patients with Crohn's disease. However, despite radical treatment, there is a risk of disease recurrence at the site of the intestinal anastomosis in some cases. Therefore, long-term postoperative management is crucial and requires systematic clinical assessment, endoscopic surveillance, and pharmacological support when indicated. A key challenge is identifying the risk factors associated with the recurrence of anastomotic failure and defining the principles of follow-up care to prevent secondary intestinal insufficiency. This paper focuses on both surgical and non-surgical factors that may play a role in preventing complications in patients undergoing ileocecal resection, providing a comprehensive approach to postoperative management.

Key Words: Crohn’s disease; Ileocecal valve resection; Ileocecal stenosis; Intestinal insufficiency; Endoscopic surveillance; Anastomotic restenosis

Core Tip: The article emphasizes the importance of long-term postoperative management for patients with Crohn's disease after ileocecal resection, as recurrence at the anastomosis site remains a risk. It advocates for systematic clinical assessments, endoscopic surveillance, and pharmacological support when necessary. The authors aim to identify risk factors for recurrence and establish follow-up principles to prevent complications, highlighting both surgical and non-surgical strategies crucial for patient care.

INTRODUCTION

Crohn’s disease (CD) is a chronic inflammatory condition affecting the entire gastrointestinal (GI) tract thickness. While it can occur anywhere along the GI tract, from the mouth to the anus, the ileocolonic region is the most frequently affected site. The inflammation in CD is characteristically discontinuous, with inflamed segments interspersed among healthy tissue. Due to its transmural involvement, CD is prone to complications such as strictures, fistulas, and both perianal and intra-abdominal abscesses[1].

CD primarily affects young individuals, including children. However, in recent years, the prevalence of inflammatory bowel diseases (IBD)—which include both CD and ulcerative colitis—has been rising among the elderly. The age-adjusted incidence rate for females varies by region, ranging from 2 to 10 per 100000 person-years, and is comparable between genders[2].

The precise cause of CD remains unknown, but it is believed to result from chronic inflammation triggered in genetically predisposed individuals with underlying immune dysregulation. This process is further influenced by environmental factors, particularly lifestyle patterns common in Western societies. Key contributors include a diet rich in processed foods, limited exposure to infectious agents, and frequent antibiotic use, especially in childhood[1].

Although CD remains incurable, significant advancements in treatment have expanded the range of available therapies. Innovative options, including biologic agents and upadacitinib, have improved disease management and patient outcomes. However, despite these therapeutic advancements, surgery remains a crucial intervention for many patients, particularly those with isolated ileocecal disease or complications such as strictures, fistulas, and abscesses[1].

Ileocecal insufficiency and anal fistulas are among the most common manifestations of CD[3]. Long-term studies indicate that despite intensified pharmacotherapy, 36% of patients with active disease require surgical intervention within five years due to intestinal complications, with one-third of these cases necessitating ileocecal and/or terminal ileum resection[4-6].

According to European Crohn's and Colitis Organization (ECCO) guidelines, the preferred approach for patients with moderate to severe abdominal CD is the initiation of biologic therapy, potentially supported by budesonide to induce intraluminal remission[7]. However, when conservative treatment fails, disease progression can lead to worsening intestinal dysfunction and metabolic deterioration, ultimately necessitating surgical intervention. Recent data suggest that up to 87% of patients with ileocecal CD eventually require surgical resection, with emergency procedures accounting for as many as 40% of cases[4,5]. As a result, an increasing number of IBD centers are adopting an earlier surgical approach as an alternative to prolonged pharmacotherapy. This proactive strategy aims to prevent complications such as obstruction and significant weight loss, ultimately improving patient outcomes[7].

Postoperative follow-up data indicate that, in some cases, inflammatory lesions recur at the anastomotic site despite radical surgery. The incidence of secondary ileocolic insufficiency ranges from 10% to 40%, and among patients with coexisting perianal disease, up to 45% may require anastomotic resection[6,8]. Given this risk, it is crucial to establish clear principles for postoperative management, tailored to the individual risk factors for CD recurrence at the anastomotic site. Both the choice of surgical technique and the effectiveness of pharmacological therapy should be carefully monitored, ensuring a personalized approach that aligns with the patient’s disease course[9].

SURGICAL MANAGEMENT

Restrained bowel resection

Surgical intervention in CD remains a secondary approach, reserved for cases where complications can no longer be managed conservatively. Given the chronic, relapsing nature of CD, surgical treatment focuses on addressing abscesses and fistulas while minimizing the extent of bowel resections[10]. For patients with multi-segment involvement, the choice between multiple limited resections with anastomoses or a single, extensive excision must be carefully considered[11,12]. In select cases, strictureplasty offers a less invasive alternative, provided there are no contraindications such as severe GI obstruction or insufficient healthy bowel segments between strictures[13].

Type of anastomosis

CD can affect any part of the GI tract; however, in nearly 65% of cases, it primarily involves the ileocecal valve and the terminal ileum. This anatomical predisposition results in slower digestive transit, prolonging the retention of intestinal contents and promoting bacterial fluctuations. Consequently, both pathogenic and opportunistic microbes proliferate, exacerbating intramural inflammation[14-16].

Current guidelines do not establish clear technical standards for performing ileotransverse anastomosis, and long-term outcomes remain difficult to assess, regardless of whether the procedure is conducted laparoscopically or via open surgery. The primary objective is to preserve the functionality of the anastomotic site while minimizing the risk of recurrent stenosis or obstruction in the years following surgery. Additionally, surgical management must aim to reduce metabolic stress and prevent malnutrition. Therefore, determining the optimal timing for surgery is crucial, particularly in balancing minimal intestinal resection with the benefits of a less invasive approach[17,18].

The primary goal of abdominal surgery in CD is to effectively manage complications such as abscesses, fistulas, strictures, and inflammatory masses, which often necessitate segmental intestinal resection[19,20]. GI reconstruction aims not only to restore continuity but also to minimize the risk of disease recurrence at the surgical site. According to current guidelines, side-to-side anastomosis remains the preferred technique, as it preserves an optimal anastomotic diameter and facilitates smooth intraluminal passage[19,21,22]. While two-row linear cutting (and swing) GI anastomosis staplers are commonly used, three-row staplers appear to offer superior outcomes in reducing the risk of leakage and bleeding[3,23].

Most recommendations favor isoperistaltic anastomosis due to its advantages in maintaining proper passage and reducing the risk of kinking. However, some surgeons advocate antiperistaltic suturing, citing its technical simplicity, shorter operative time, and cost-effectiveness, which may contribute to its preference in certain centers[14,24].

An alternative strategy for GI reconstruction was introduced by Torou Kono, who first performed the antimesenteric end-to-end (Kono-S) anastomosis in 2003[25]. The primary advantage of this technique is the formation of a supporting column from the proximal and distal bowel segments remaining after resection. The Kono-S modification more effectively separates the mesentery from the suture line, thereby reducing the risk of secondary infiltration at the anastomotic site. However, this technique typically involves hand suturing and requires at least 10 cm of healthy bowel ends, which limits its applicability in laparoscopic procedures[25-27].

In the early 2010s, some authors highlighted the benefits of the Kono-S anastomosis, particularly in minimizing postoperative complications and recurrence rates. In a study by Kono et al[28], no cases of secondary anastomotic failure were observed in a cohort of 187 patients between 2003 and 2011, with a median follow-up of 32 months[27,28]. Similarly, Luglio et al[29], in a meta-analysis of 12 studies involving 820 patients, reported a recurrence rate of 24.1% for endoscopic recurrence and 3.9% for surgical recurrence after a median follow-up of 22.8 months[29]. In the short term, the Kono-S anastomosis appears to be relatively safe, with complications comparable to those seen with alternative anastomotic techniques[30]. However, the limited number of randomized controlled trials involving a large patient cohort hampers the development of definitive recommendations for surgical management.

Type of approach

Modern surgery for CD is increasingly characterized by the adoption of laparoscopic procedures. The main advantages of this approach include reduced perioperative trauma, less inflammatory response, and a lower risk of metabolic deficiencies[10]. Visual enhancements, such as screen magnification, 3-D imaging, and blood perfusion detection using indocyanine green, further improve surgical precision and the quality of anastomoses[12,31].

However, patients with advanced abdominal complications, such as fistulas or inflammatory masses—especially those infiltrating adjacent tissues—are typically excluded from laparoscopic surgery. Similarly, cases involving multisegmental bowel strictures or (sub)ileus are less suitable for minimally invasive procedures due to insufficient pneumoperitoneum and limited space for surgery[32].

Therefore, laparoscopy is most beneficial in the early stages of intestinal disease. According to ECCO guidelines, it may serve as an alternative to infliximab therapy[19]. This approach necessitates disciplined surveillance of patients undergoing pharmacological treatment, with timely transition to radical interventions when conservative measures fail. Ultimately, the decision should involve collaboration between the surgeon, gastroenterologist, radiologist, dietitian, and psychologist[33].

CONSERVATIVE THERAPY

Prevention of anastomotic strictures

The decision to initiate new pharmacological treatment or continue the current regimen in CD patients following segmental bowel resection should be guided by the individual risk of disease recurrence. Based on the severity of relapse risk, two primary strategies are recommended: Proactive and reactive. The proactive strategy involves implementing prophylactic treatment immediately after surgery, while the reactive strategy focuses on treating inflammatory lesions at the anastomosis site, which are diagnosed endoscopically within 6-12 months post-surgery[34,35].

Ileocolonoscopy with assessment of the anastomosis using the Rutgeerts score remains the gold standard. While less invasive tests, such as magnetic resonance enterography, intestinal ultrasound, and fecal calprotectin concentration, are also valuable, their role in postoperative follow-up remains uncertain[34,36].

The reactive strategy is still the most commonly used approach worldwide. However, its main limitation lies in the risk of disease progression, particularly in patients with an unfavorable long-term disease course. Therefore, the proactive strategy may be especially beneficial for patients under 30 years of age, smokers, those who have already undergone surgery, or individuals with a penetrating phenotype of the disease. Recent data suggest that the benefits of reducing the risk of both endoscopic and clinical recurrence outweigh the potential adverse effects of prophylactic therapy. In fact, proactive treatment should be started as early as 2-4 weeks after surgery, provided a positive clinical response is anticipated[34,35]. The key features of the proactive approach are summarized in Table 1.

Table 1 Advantages and disadvantages of proactive pharmacologic strategy for Crohn’s disease patient post-ileocecal resection, and proposed qualification criteria.

Qualification criteria	Advantages	Disadvantages
History of multiple bowel resections	Lower risk of disease recurrence	Higher cost
Perianal involvement	Lower risk of disease-related complications	Risk of overtreatment
Penetrating disease behavior
Patients under 30 years old
Smokers
Presence of granulomas in resection specimen
Presence of myenteric plexitis

Postoperative management for both proactive and reactive patients focus on the appropriate administration of pharmacotherapy, particularly thiopurines and/or biologics, which remain the most effective therapeutic options. Current studies show that patients who are naïve to immunosuppressive treatment, as well as those receiving TNF-α inhibitors, respond most effectively to this therapy and are more likely to achieve long-term remission. However, in certain cases, alternative biologic drugs such as vedolizumab or, to a lesser extent, ustekinumab, may be considered[35,37].

Bacterial etiology of CD

Previous research has shown statistically significant differences between the microbiotas of individuals with CD and healthy controls, suggesting that dysbiosis may play a crucial role in triggering IBD. Patients with newly diagnosed CD typically exhibit an increased presence of Proteobacteria colonies and a decreased abundance of Bacteroides and Firmicutes species[38]. A well-documented cause of intestinal inflammation is the disruption of the protective mucosal epithelium by specific Proteobacteria, including E. coli, particularly adherent-invasive E. coli[39].

Microbial profile after surgical resections

Clinical reports on postsurgical fluctuations of intestinal microbes indicate that the lymph nodes of patients undergoing intestinal resections commonly present Enterococcal species, Bacteroides fragilis, and Clostridium perfringens compared to healthy controls. Similar findings have been observed in mucosal biopsies taken during postoperative endoscopic surveillance. After ileocecal valve resection, the mucosa was predominantly enriched with members of the Proteobacteria family, in contrast to a decrease in Staphylococcaceae, Streptococcaceae, Bifidobacteriaceae, Clostridiaceae, and Pseudomonadaceae. Additionally, in CD patients with recurrent ileocecal disease, 6 to 18 months postoperatively, the intestinal microbiota was characterized mainly by proteolytic fermentation and lactic acid-producing bacteria such as Enterococcus and Veillonella species. This contrasted with the typically predominant genera such as saccharolytic Bacteroides, Prevotella, Parabacteroides, and Firmicutes[40].

Indications and type of antibiotic therapy

Following these findings, new strategies have been designed to assess the efficacy of antibiotic therapy in patients with relapsed CD. Assessing the risk of recurrence is crucial for clinical decision-making in patients with postoperative CD. The Postoperative Crohn’s Endoscopic Recurrence study categorized patients into low- and high-risk groups for postoperative recurrence. The high-risk group consisted of patients with perforating disease (such as abscesses, intestinal fistulas, or free perforations) and a history of at least one previous intestinal resection. This group also included smokers. All patients received metronidazole, while high-risk patients were also treated with thiopurines or adalimumab in cases of thiopurine intolerance. Colonoscopy was performed in both groups after six months, and based on the findings, adalimumab was added to the initial metronidazole and thiopurine treatment in the high-risk group. Alternatively, the frequency of adalimumab administration was increased to once a week for those already receiving it every two weeks. This approach was termed "active CD therapy". The study showed that 51% of high-risk patients treated with active care remained in endoscopic remission (i0–i1), compared to 70% of high-risk patients treated with standard care who were diagnosed with recurrent disease[41,42].

Another suggestion proposed by Rutgeerts et al[43] is the simultaneous use of metronidazole and ornidazole as a curative treatment for limiting inflammation. A similar study demonstrated that all patients received metronidazole for one month, along with either azathioprine or a placebo for one year. Compared to the azathioprine or placebo group, patients treated with metronidazole had a lower risk of recurrence. Thus, a low dose of metronidazole (250 mg three times daily for 3 months) could be a promising solution for inhibiting postoperative relapses[44-46]. The administration of imidazole antibiotics also showed some benefits following treatment, although previous studies were limited by adverse events and drug intolerance.

However, other studies investigating ciprofloxacin therapy for the prevention of postoperative recurrence in CD patients failed to demonstrate a statistically significant advantage compared to placebo[47].

Effectiveness of probiotics

The effectiveness of certain probiotics in modifying the course of IBD has been demonstrated in animal and in vitro studies, but reliable human trials are still lacking. One probiotic that has been cautiously recommended for CD patients is VSL#3, which consists of eight bacterial strains: Four strains of Lactobacillus, three strains of Bifidobacterium, and one strain of Streptococcus. This commercial mixture has been found to limit immune responses and counteract endoscopic recurrences, particularly in adults undergoing ileocecal resections[48]. Other studies have explored the role of probiotics in inducing CD remission, such as Lactobacillus rhamnosus strain GG and synbiotic therapy, which combined freeze-dried Bifidobacterium longum with a commercial product. Despite promising results, these studies did not show statistically significant differences compared to placebo[49].

Endoscopic management

Advances in endoscopic imaging technologies have significantly enhanced the visualization capabilities, providing IBD patients with the benefits of early disease detection and monitoring treatment response. Ileocolonoscopy, which includes intubation of the terminal ileum and optional biopsy, is a key component of the initial evaluation for most patients with suspected CD. Endoscopy is considered the gold standard for assessing anastomosis or the neoterminal ileum following surgical resection[50].

Endoscopic surveillance

According to the American Gastroenterological Association guidelines, postoperative endoscopic monitoring is recommended 6–12 months after surgery for both patients on and off postoperative medical therapy for CD[51]. This strategy is closely linked to the concept of post-operative therapy, often referred to as endoscopy-driven prophylactic therapy, which begins after confirming endoscopic postoperative recurrence. The recurrence rate in patients who have undergone ileocecectomy can be as high as 70% within the first year[52,53]. The most widely used scale for evaluating endoscopic lesions in CD is the CD Endoscopic Index Score, which categorizes mucosal abnormalities from superficial lesions to strictures with ulcerations. For patients after surgical resection, ileocolonoscopy should routinely assess the anastomosis and neoterminal ileum. Traditionally, the Rutgeerts score has been used to estimate endoscopic findings, but the recently proposed REMIND score by Hammoudi et al[54] may offer a more appropriate approach by separately describing anastomotic and ileal lesions (presented in Table 2).

Table 2 Detailed description of REMIND score according to Hammoudi et al[54].

REMIND score
Anastomotic lesions (< 1 cm in length after the anastomosis)
A(0)	No lesion
A(1)	Ulcerations covering less than 50% of the anastomosis circumference
A(2)	Ulcerations covering more than 50% of the anastomosis circumference
A(3)	Anastomotic stenosis
Ileal lesions
I(0)	No lesion
I(1)	≤ 5 aphthous ulcers
I(2)	> 5 aphthous lesions with normal intervening mucosa or skip areas of larger lesions
I(3)	Diffuse aphthous ileitis with diffusely inflamed mucosa
I(4)	Diffuse inflammation with larger ulcers

The main objective in the postoperative follow-up of CD patients after ileocecal resection is the early detection of anastomotic failure and the standardization of diagnostic criteria for ileal insufficiency. Some authors define surgical recurrence solely as the need for anastomosis re-resection, even though endoscopic surveillance clearly shows that repeated ileocolic insufficiency develops much earlier[9,55]. Therefore, direct endoscopic examination, described using dedicated scales, often detects clinically unnoticeable intestinal insufficiency. As a result, some reports likely underestimate the total number of anastomotic failures because they do not account for endoscopic manifestations that are clinically controlled through medications and dietary management[41,56].

Minimally invasive therapy

Endoscopy with contemporary devices offers several treatment options for ileal or anastomotic strictures, which are common complications of CD. The choice of treatment method depends on the clinical presentation of the stricture and its anatomical characteristics on endoscopy, particularly the length and degree of luminal narrowing. Among the available options, endoscopic balloon dilation has become the most widely used modality, recognized as a safe and effective technique for managing postoperative strictures. Other approaches, such as endoscopic stricturotomy, endoscopic strictureplasty, and self-expanding metal stents, should be considered in patients with strictures accompanied by deep ulcerations. Regardless of the treatment method chosen, complications such as bleeding and perforation of the digestive tract may occur and should be anticipated[57,58].

IMPACT OF METABOLIC EFFICIENCY

Risk related to malnutrition

Reduced oral intake, malabsorption, and chronic inflammation, in relation to increased metabolic demands, contribute to nutritional depletion in patients with CD (57). The European Society for Clinical Nutrition and Metabolism categorizes malnutrition into three types based on etiology: Disease-related failure with or without inflammation, and malnutrition without disease, highlighting the impact of comorbidities and immune response on the metabolic condition[59].

Protein-energy malnutrition specifically impairs the patient’s ability to repair tissues, maintain immune function, and recover after surgery[60]. Metabolic deficiency is also linked to an increased risk of perioperative mortality, mobility limitations, and poor health status[61]. Stenosis, narrowing, and fistulas are common complications of CD, often correlating with poor metabolic condition[62,63]. A lack of protein can particularly hinder tissue repair, leading to anastomotic leaks and fistula formation[17]. Chronic malabsorption, compounded by perioperative starvation, limits the availability of crucial amino acids necessary for collagen synthesis and wound healing[64]. Consequently, malnutrition in this group of patients contributes to a higher risk of recurrent stenosis and the need for secondary surgical interventions[33,65,66].

To mitigate the risk of postoperative CD relapses, all patients qualifying for surgery should have improved nutritional status through the provision of oral supplements, enteral nutrition, and, if necessary, parenteral nutrition. Ongoing monitoring of metabolic markers and early intervention are crucial for preventing malnutrition and reducing the risk of post-surgical complications[33].

CONCLUSION

The management of CD patients requires interdisciplinary, long-term therapy, with outcomes heavily influenced by relapses and remissions. Surgical treatment primarily focuses on the definitive removal of abdominal complications such as abscesses, fistulas, and strictures contributing to obstruction. However, there are proponents of elective surgery in the early stages of bowel disorders. Additionally, patients with ileocecal valve failure and focal inflammatory lesions may benefit more from radical procedures than from prolonged conservative treatment. The gold standard in surgical approaches remains limited bowel resection with a wide, side-to-side stapled anastomosis. Laparoscopic surgery has advantages over open surgery, particularly due to less trauma and a more favorable metabolic balance. To prevent recurrence, regular clinical monitoring and endoscopic surveillance, classified according to the Rutgeerts or REMIND scores, are essential. In patients at high risk of relapse, especially those with the penetrating phenotype of CD or a history of previous surgeries, prophylactic therapy with immunosuppressives and biologics should be considered based on the severity of clinical symptoms and endoscopic assessment. Collaborative care involving a multidisciplinary team—including dietitians, gastroenterologists, and surgeons—is critical to ensure comprehensive management. Therefore, the demand for funding specialized medical centers is essential for providing comprehensive treatment for IBD patients.