Anastomotic leak after ileocolic resection for Crohn’s disease: The latest evidence

Abstract

Studies have indicated that approximately half of individuals with Crohn’s disease (CD) may undergo surgery at some point during their lifetime. Ileocolic resection (ICR) is the most frequently performed procedure for treating CD. Addressing anastomotic leak (AL) remains a critical focus in the perioperative and postoperative care of CD patients. A research study published in the World Journal of Gastrointestinal Surgery by Cwaliński et al included 77 individuals who had open ICR and primary stapled anastomosis to assess the risk factors linked to anastomotic insufficiency. At present, research on anastomotic insufficiency has focused on AL. Therefore, this editorial mainly analyzes the current risk factors linked to AL after ICR and discusses potential prevention strategies. We comprehensively consider risk factors such as body weight, medication use, surgical history, smoking, penetrating behaviour, and albumin levels to stratify patient risk. Based on recent research insights, we propose that individualized surgical timing, approaches, and techniques should be selected according to the patient's risk level.

Key Words: Anastomotic leak; Risk factor; Ileocolic resection; Prevention; Crohn’s disease

Core Tip: Anastomotic leak (AL) frequently occurs as a complication following ileocolic resection. Early warning of its high-risk factors facilitates the adoption of effective, targeted strategies to mitigate the occurrence of AL and optimize surgical quality. The prevention of AL plays a crucial role in the postoperative management of Crohn's disease, contributing significantly to patient outcomes.

INTRODUCTION

Crohn's disease (CD) is a persistent inflammatory condition affecting the gastrointestinal tract. It can lead to complications like strictures, fistulas, or abscesses, potentially requiring surgical intervention. The most common surgical procedure for individuals with CD is ileocolic resection (ICR)[1]. Anastomotic leak (AL) is a prevalent postoperative complication, and it occurs in 1.2% to 16.7% of CD patients undergoing surgery[2]. Nevertheless, AL after intestinal resection remains a significant unresolved challenge in treating CD. The occurrence of AL or intra-abdominal abscess within 90 days after ICR may elevate the likelihood of endoscopic and surgical postoperative recurrence in CD[3]. Perforating diseases like fistulas can elevate the incidence of septic complications and impact surgical outcomes in CD[4]. Cwaliński et al[5] conducted an observational study on 77 individuals who had open ICR and primary stapled anastomosis in their article entitled "Surgical and nonsurgical risk factors affecting the insufficiency of ileocolic anastomosis after first-time surgery in Crohn’s disease patients". They analyzed risk factors linked to anastomotic insufficiency, such as prolonged postoperative obstruction, anastomotic bleeding, and clinically confirmed micro-leakage. Therefore, exploring risk factors of AL after ICR seems requisite and facilitates the development and utilization of therapeutic strategies for treatment and prevention. This article synthesizes the latest evidence on potential risk factors for AL and highlights strategies to reduce its occurrence. The literature search of all articles published between 2019 and 2024 was conducted using PubMed, focusing on studies that provided high-quality evidence. Systematic reviews, randomized controlled trials, meta-analyses, and clinical trials were eligible for inclusion.

RISK OF AL

The incidence of AL in patients with CD exhibits considerable variability across published studies, with incidence rates varying between 1.5% and 12.1% as reported (Table 1). Hence, identifying potential risk factors for AL is crucial. In some recent literature, several risk factors of AL have been identified, although some are still being debated (Table 1). The role of biologic exposure as a risk factor remains controversial[6]. Gklavas et al[7] found that anti-tumour necrosis factor (anti-TNF) monotherapy or combination therapy has no association with postoperative morbidity. A retrospective single center study recently showed that preoperative biologic therapy in CD is not linked to AL following ICR[8]. Notably, no association was found between the timing of anti-TNF-α administration and the occurrence of postoperative outcomes[9]. Patients should not be denied surgery because of only the anti-TNF therapy status but should be carefully monitored postoperatively for complications[10]. Therefore, biologic therapy tends to be discontinued 3-4 weeks or longer prior to elective surgeries[11]. It is also recommended to initiate their use 3-6 weeks post-resection[1]. Gene expression signatures may help predict anastomotic healing of CD. Animal experiments confirm that anastomosis is impaired in nucleotide-binding oligomerization domain-containing protein 2 (NOD2)-deficient mice[12]. However, clinical trials show that there is no evidence demonstrating clear connection between homozygosity for the NOD2 high-risk variant p.Leu1007fsX1008 and postoperative complications[13]. A recently released retrospective study, which compared CD patients who underwent ileocolic anastomosis with non-CD patients, revealed an intriguing finding: CD is considered as a disease-specific risk for impaired anastomotic healing[14].

Table 1 Risk factors of anastomotic leak in Crohn’s disease patients.

Ref.	Outcome	Incidence	Risk factors
Neary et al[50]	AL	Primary anastomosis 4.5%; anastomosis plus ileostomy 2.7%	Ileostomy omission, emergency surgery, smoking, inpatient status, wound classification 3 or 4, weight loss, steroid use, and prolonged operative time
Jeganathan et al[62]	AL		Low serum albumin, preoperative abscess, prior abdominal surgery, and steroid use
Yoon et al[63]	Septic complications	7.6%	Use of any immunosuppressive medication
Zager et al[55]	AL	6.5%	Lower mean psoas muscle area
Schweer et al[14]	AL	12.1%	CD
Avellaneda et al[64]	AL	CCD group 5%; ICD group 2.2%	CCD
Dajti et al[65]	IASCs	IASCs 6.6% (AL 3.8%)	Low preoperative serum albumin levels and use and dosage of preoperative oral budesonide
Fichera et al[66]	Anastomotic failure1	1.5%
Lavorini et al[67]	AL	5.2%	Steroids and increased interval between diagnosis and surgery
Yang et al[20]	AL	Primary ICR 2.9%; Redo ICR 3.5%	Extensive adhesiolysis, ileostomy omission, and intraoperative fistula/abscess
Celentano et al[37]	AL	3.7%	ASA grade ≥ 3, presence of perianal disease, and ileocolonic localization of disease

¹Anastomotic failure was defined as radiographic evidence of a leak from the anastomosis or the presence of an intra-abdominal abscess adjacent to the anastomosis. Septic complications: anastomotic leaks and/or abscess.

IASCs: Intra-abdominal septic complications (anastomotic leak, abscesses, and entero-cutaneous fistula); AL: Anastomotic leak; CD: Crohn's disease; CCD: Complicated Crohn's disease; ICD: Uncomplicated inflammatory Crohn's disease; ICR: Ileocolic resection; ASA: American Society of Anaesthesiologists.

PREVENTION OF AL

Timing and number of surgeries

The importance of early surgery in CD patients is increasing. However, it is difficult to find a universally agreed-upon definition for early surgery. Some past reports define early surgery as surgery within 1 year of diagnosis, while recent studies focus more on disease evolution[15]. Patients undergoing resection with the inflammatory luminal component have a more beneficial outcome than patients with stenotic or penetrating complications[16,17]. In patients with complicated CD, early laparoscopic ICR (≤ 7 days) without abscess drainage is safe and may not raise postoperative complication risks[18]. Although iterative ileocolonic resection elevates the likelihood of non-infectious complications, particularly ileus, it does not affect intra-abdominal septic complications (IASCs), AL rate, severe postoperative complications, and reoperation with or without stoma co-infection. Therefore, iterative ileocolonic resection may be an option for recurrent CD, and its use should not be refused due to complications[19]. Further experiments have revealed that extensive adhesiolysis, the omission of ileostomy, and the presence of intraoperative fistula or abscess are related to AL in multivariate analysis, whereas iterative ICR is not[20].

Surgical approach

Minimally invasive surgery (MIS) serves as the primary method for treating CD[6]. The benefits of MIS compared with open resection have been well documented, such as decreased need for analgesia, reduced hospital stay, and lower hospital costs[21,22]. A previous meta-analysis confirmed that laparoscopic surgery for recurrent CD is feasible and safe, without elevating the risk of postoperative complications[23]. As laparoscopy becomes more widely utilized, open surgery is now primarily reserved for situations where a laparoscopic approach is not feasible, such as abdominal wall involvement, concomitant open procedure, and anesthesiologic contraindication to MIS[24]. When compared with multi-port laparoscopy, single-incision laparoscopic surgery has several advantages including better cosmetic outcomes[25], shorter operative time, and shorter hospitalization time without increased risk for complications such as AL and postoperative wound infections[26]. Moreover, although laparoscopic access has been widely accepted for colonic surgery, there are inherent limitations of laparoscopic platforms in narrow pelvic operations. Owing to a three-dimensional visual perspective, stable camera platform, better dexterity capability, and enhanced ergonomics, the robotic platform can potentially address some limitations of conventional laparoscopic surgery[27]. The safety and feasibility of robotic use in CD patients and even complicated CD patients undergoing ICR have been confirmed[28,29]. However, there are still open issues and challenges due to its high cost and long operative time[30,31].

Anastomotic techniques and configurations

In terms of intestinal reconstruction, an intracorporeal (ICA) or extracorporeal (ECA) anastomosis is performed. However, there are relatively few studies on these two anastomosis methods for CD. A study conducted by Calini et al[32] retrospectively analyzed robotic ICR for CD in patients who underwent ICA or ECA. The results indicated a quicker restoration of bowel function in the ICA group, with no significant differences observed between the groups in terms of ileus, hospital stay, or overall complication rates. Similar findings were observed in the comparison of robotic ICA and laparoscopic ECA. Robotic ICA was associated with improved short-term postoperative outcomes, including reduced hospital stay, decreased complication rates, and accelerated bowel function recovery[33]. Further multiple center randomized controlled studies are needed to validate these findings and evaluate the long-term outcomes.

In general, there were two approaches for restoration of bowel continuity following intestinal resection, stapled and handsewn anastomoses. The results of studies published comparing the outcomes of stapled vs handsewn anastomoses in CD have been somewhat conflicting[34-36]. A retrospective analysis conducted by Lahes et al[34] that investigated early postoperative complications and surgical outcomes following bowel resection in CD found no significant distinction between stapler anastomosis and handsewn anastomosis. Notably, a retrospective, multicenter study in Italian showed no association between AL and the type of anastomosis[37]. In a meta-analysis comparing outcomes between stapled side-to-side anastomosis and handsewn end-to-end anastomosis (HEEA), HEEA was associated with increased AL rates[36].

There are few comprehensive studies on suturing methods. Oversewing stapled ileocolic anastomoses was confirmed to reduce the odds of AL and reoperation due to septic complications[38]. However, no significant difference in AL was detected between the interrupted suture approach and the continuous suture method[39].

The current literature remains inconclusive regarding the effect of Kono-S anastomosis (KSA) technique on surgical complications[40-42]. Baloyiannis et al[40] assessed eight studies between 2011 and 2023 comparing 418 patients undergoing KSA vs 495 patients who received conventional anastomosis (end-to-end anastomosis, end-to-side anastomosis, and side-to-side anastomosis). The Kono-S group exhibited a lower risk of AL and the need for reoperation compared to the conventional anastomoses group. Conversely, some studies have reported no significant difference in the occurrence of AL between the KSA group and conventional anastomosis[41,42].

Mesenteric excision

Recent research increasingly emphasizes the importance of the mesentery in the development of CD[43]. Some surgeons have already performed both localized and extensive mesenteric resection in CD patients. Compared with mesentery preservation, Coffey et al[44] showed that mesentery excision is associated with reduced recurrence requiring reoperation in CD patients undergoing ICR. Another study suggests that mesenteric removal does not seem to minimize the likelihood of recurrences and complications[45]. The variability of patients and the limited sample sizes in various studies could be the causes of the contradictory results. Recently, an acceptably low rate of IASCs and leak has been found in the mesenteric excision and exclusion (MEE) group which combines the KSA and extended mesenteric excision techniques[46,47]. Future studies with extended follow-up periods are needed to verify postoperative results of MEE.

Fecal diversion

In CD patients who are at high risk of anastomotic failure, fecal diversion following intestinal resection emerges as a reliable and efficacious therapeutic approach[48,49]. Diverting ileostomy can reduce potential AL based on individualized risk stratification, especially if there are ≥ 3 risk factors[50]. The decision to perform fecal diversion on CD patients needs to be made carefully due to the risks of stoma reversal[51]. In high-risk CD patients, AL rate, anastomotic bleeding rate, and anastomotic stricture rate were lower for split stoma with delayed anastomosis compared with primary anastomosis with protective stoma[52].

Perioperative management

Preoperative enteral nutrition has been shown to decrease the overall incidence of postoperative complications, especially septic complications[53]. Research indicates that individuals who undergo personalized prehabilitation (PP) before ICR can mitigate preoperative risk factors and potentially lower the rate of anastomotic complications[54]. PP encompasses a range of treatments, such as providing nutritional assistance, adjusting corticosteroid therapy, and addressing intra-abdominal sepsis. Endoscopic recurrence often precedes clinical symptoms. Therefore, regular postoperative endoscopic examination with Rutgeerts scoring is crucial. It is typically recommended to perform this examination 6 to 12 months after resection, with earlier examination advisable for individuals with more aggressive disease phenotypes or those who have undergone multiple resections[1].

Other factors

The exact role of muscle and fat tissue in AL after surgery for CD is not clearly understood. Zager et al[55] retrospectively included CD patients who had bowel resection and preoperative computed tomography/magnetic resonance imaging (MRI) scans. As an effective tool for the measurement of sarcopenia, low psoas muscle area values are significantly related to postoperative complications, including AL, paralytic ileus, and pneumonia. However, solely relying on MRI-based evaluations of myopenia and myosteatosis is insufficient for predicting postoperative outcomes or recurrence rates in CD patients[56]. This controversial finding may be attributed to the insufficient availability of convincing, age-related, objective criteria for assessing myopenia. In addition, studies have demonstrated that visceral adiposity is not associated with AL or CD recurrence[57]. Moreover, C-reactive protein level, mucosal microbiota, and histologically inflamed resection margins are possible to become new predictive biomarkers for AL in patients with CD[58-60]. When it comes to treating AL, endoscopic procedures such as fistulotomy, clipping, and drainage, as well as surgical intervention, are viable options[61].

CLINICAL IMPLICATIONS

Early intervention serves as an effective approach in treating postoperative AL. Therefore, it is crucial to thoroughly understand the risk factors linked to AL in CD patients. Effective management of AL necessitates considering a multitude of factors, such as body weight, medication use, surgical history, smoking, penetrating behaviour, and albumin levels[14,20,37,50,55,62-67]. These considerations allow for the formulation of a rational and personalized surgical treatment plan, ultimately optimizing clinical outcomes for CD patients. There are still outstanding questions that need to be addressed in future studies, including the biologic exposure and selection of surgical timing.

CONCLUSION

AL continues to be a significant and potentially fatal complication following colorectal surgery in CD patients. This editorial highlights the need to develop precautionary measures to prevent anastomotic insufficiency, especially AL. Identification of risk factors, as well as advances in surgical techniques and perioperative management, is an essential step in reducing disease burden. These factors may potentially aid in stratifying patient risk and guiding treatment decisions. The etiology of AL is multifactorial, and the development of risk prediction models, along with the exploration of interrelationships among these factors, may emerge as key areas of focus in future research.