Clinical outcomes and perioperative morbidity and mortality following segmental resections of the colon for Crohn’s colitis

Crohn’s disease (CD), first described by Crohn et al. [1] in 1932, is a chronic inflammatory bowel disease leading to discontinuous inflammation of the gastrointestinal (GI) tract [2, 3]. Typically, patients experience symptom-free intervals, alternating with periods of disease activity. In general, disease manifestation can be found throughout the whole GI tract, with the terminal ileum being the most common site. About 25% of patients show an isolated affection of the colon leading to Crohn’s colitis, which needs to be thoroughly differentiated from ulcerative colitis [4].

Chronic recurrent inflammation can lead to disease-specific complications. Stenosis, fistulas, abscesses or inflammatory tumours are common complications that up to 50% of patients might develop over time.

Despite a conservative therapeutical approach with monoclonal antibodies (MAB), disease-modifying antirheumatic drugs (DMARDs) or steroids, being the first choice for patients diagnosed with CD, a large proportion of patients will still need surgical intervention at one point [2‐7]. However, surgical procedures are a challenge due to the underlying inflammation and morbidity rates as well as rates for disease recurrence are high [2, 4, 8]. Patient populations have been analysed for possible risk factors leading to higher morbidity in case of CD-associated surgeries. The current literature states duration of the disease, length of the resected intestinal segment, preoperative medication or specific phenotypical findings as possible risk factors for higher perioperative morbidity and mortality [2, 8‐10]. The role of underlying genetic alterations such as mutations in the NOD2 gene, which are associated with a more aggressive phenotype of CD, remains controversial [3]. Some authors describe no influence on the postoperative course after ileocolonic resections [2], whereas others show a negative predictive role of the mutation on the perioperative outcome after ileocolectomy [11].

Within the group of CD patients needing surgery, colonic resections are not very common which leads to a lack of information on morbidity and mortality after CD-associated colonic resections.

Therefore, the aim of the current study was to analyse rates for perioperative morbidity and mortality and to evaluate possible risk factors for postoperative complications and disease recurrence specifically in case of colonic resections for CD compared to ileocaecal resections (ICR).

A total of 241 patients, 127 males (52.5%) and 114 females (47.5%), were included in the study. Mean age at the time of surgery was 42.74 years (± 15.25 years) and mean age at diagnosis of CD was 29.90 years (± 14.47 years), leading to a mean duration of disease of 11.86 years (± 8.63 years) between first diagnosis and current surgery. Mean follow-up after surgery was 68.9 months (± 47.48 months), with data being available for 191 patients (79.3%). Data on previous medical conditions, prior abdominal surgeries and pre- and postoperative medical therapy is available in Table 1.

89.6% (n = 215) of patients underwent elective surgeries, whereas 10.4% (n = 25) had an emergency procedure. Data on the primary surgical approach was available for 233 patients. 69.1% (n = 161) of procedures were performed primarily with an open approach, and 30.9% (n = 72) were performed laparoscopically. The rate of laparoscopic procedures was significantly higher in the case of ICR (p < 0.001). Conversion to an open approach was necessary in 22.54% (n = 16), 11 times for ICR, in 4 cases of colonic resections and one time for a combined resection (p = 0.058). The majority of patients received a handsewn anastomosis (87%, n = 167). Twenty-five (13%) anastomoses were stapled, 12 for ICR and 13 for colonic resections (p = 0.874).

Mean duration of surgery was 168.2 min (± 86.05 min). Mean time between hospital admission and surgery was 3.59 days (± 4.98 days).

Most frequent indications for surgery were stenosis in 59.9%, septic complications and fistulas in 12.1%, perforation in 7.8% and abscess formation in 7.3%. Less frequent reasons for surgery were conglomerate tumours in 3.4% and carcinomas in 3.9%.

Fifty-six percent (n = 135) of all patients included underwent colonic resections, whereas 44% (n = 106) underwent ileocaecal resection. Forty-one patients (17%) received a primary stoma, 26 patients due to severe inflammation. Two patients received a stoma as they underwent low anterior resection, and three patients received a definite ostomy due to rectal extirpation. In 10 cases, the reason for a temporary stoma was not documented.

Details on all surgical procedures are shown in Table 2.

Crohn’s disease as one of the two chronic inflammatory bowel diseases most commonly affects the ileocecal region [19]. About one quarter of patients show an isolated involvement of the colon [4]. Based on the frequency of performed surgeries, our study population including 43.98% ileocecal resections, 35.27% right hemicolectomies and 11.57% distal colon resections is representative for this condition and aligns with previous studies [2, 13‐15].

In Crohn’s disease, periods of inflammation usually alternate with less severe or no disease activity. Disease activity frequently results in complications such as stenosis, abscess or fistula. The latter inevitably resulted in the need for surgery, despite advancements in medical treatment options. Besides, the short- and long-term results of the LIR!C trial suggest potential benefits for selected Crohn’s patients with early surgical intervention prior to possible complications [17, 18], Therefore, there is an increased emphasis on the outcomes following surgery.

ICR is certainly one of the main surgical procedures among CD patients, and results on possible influencing factors on surgical results have been well described in the literature [13‐16]. However, colon resections might be necessary in case of colonic involvement.

Among the whole study population, 75.9% (n = 183) experienced no or only minor complications, whereas 23.1% (n = 56) had major complications after surgery.

In our study, we found more major complications after colon resections compared to ICR. Especially postoperative bleeding, the need for re-do surgery and readmission to ICU and/or hospital occurred more frequently. However, anastomotic leakage was not increased among colonic resections compared to ICR. Further analysis revealed distal resections as a risk factor for higher perioperative morbidity as well as for re-do procedures, secondary stoma and ICU admission. Presumably due to the small number of cases in our study population, these influences could not be confirmed in the multivariate analysis. Previously, Landerholm and co-workers showed in their study that colonic anastomosis are a significant risk factor for septic complications [26]. These findings suggest that colonic involvement in CD, especially distal involvement, represents a more complicated phenotype, leading, in combination with more complex surgical procedures, to higher rates of complications itself.

Further, we could identify two independent risk factors for high morbidity following colonic resections, the interval between hospital admission and surgery and the duration of surgery. These findings are in accordance with the results by Kanazawa et al. [29]. Likewise, did some groups state a reduced nutritional status, penetrating disease such as abscess or fistula and preoperative steroid use as risk factors for a complicated postoperative course [26‐29]. The two risk factors identified in our study, interval to surgery and duration of surgery, support these results as they implicate a possible reduced patient status at hospital admission as well as complex surgical site as possible reason for the delay and a prolonged operating time. Due to evolving conservative therapeutic options, patients with Crohn’s disease are often treated for long periods of time, leading to an immense impairment of their general state of health. Although delay of surgery is used to improve general condition, previous years of chronic inflammation and malabsorption cannot be entirely eliminated. In case of a severe phenotype of CD, possibly involving multiple intestinal segments, especially sufficient nutrition should be focused on, not only during a short time period prior to surgery but also during medical therapy. The latter could possibly lead to a reduction of cases needing surgery in a severe nutritional and inflammatory status.

Additionally, previous bowel resections, which we could identify as a risk factor for major complications after colonic and ileocaecal resections, also often lead to a more complex surgical site. These results are in concordance to the findings by Crowell and colleagues as well as by Duan et al. [27, 29]. Further, a former study from our own group also accounted these findings among patients with isolated ICR [2]. On the other hand, Yamamoto et al. could not confirm a relation between prior intestinal resections and postoperative morbidity [28]. Moreover, a study by Aaltonen and coworkers found emergency procedures to be a risk factor for perioperative complications, which our findings did not confirm [19]. However, our own current study and several previous studies from other groups suggest that the above-described factors, delay of surgery, duration of surgery and emergency procedures, are a surrogate for an underlying severe phenotype of CD. The latter might lead to an increase in perioperative morbidity, especially in combination with complex surgical procedures involving the distal colon [25, 27, 29].

Preoperative medication could not be confirmed as a risk factor for higher perioperative morbidity among patients after colonic resections in our study. Although univariate analysis showed an impact, this effect could not be affirmed in the multivariate analysis. These findings are in line with results by Iesalnieks et al. [21]. However, in the literature, steroid use in general is considered a risk factor for a complicated perioperative course [22, 24]. Bernstein et al. described pre- and postoperative steroid use as a clear risk factor for perioperative complications, especially that long-term steroid therapy is considered to be a relevant factor [20, 22]. As data on duration of steroid therapy was limited in our patient population, we could not perform further analysis regarding this aspect. Regarding the perioperative use of immunomodulatory drugs, there is still a controversial discussion present [24]. Our current study, like results by Kumar and coworkers, did not show any influence on perioperative morbidity [23]. Yet, other groups, like Landerholm et al., showed a significant impact of thiopurine use on the postoperative rate of anastomotic insufficiencies. Fumery et al., as well as Shah et al., also showed no association between preoperative use of monoclonal antibodies and postoperative complications [31, 32]. In general, results regarding the influence of immunomodulatory drugs on the perioperative outcome are heterogeneous.

Information on genetic alterations was only available for a subgroup of patients, and the rate for NOD2 mutations was 7.8% in the whole population. Therefore, possible conclusions are limited. Out of all patients with a detected NOD2 mutation, only 4 (1.7%) developed major complications, whereas the rest did not have any or only minor problems postoperatively. This proportion is below that of the overall study population, even if the significance of such small numbers of patients is limited. Comparable results were shown in a previous study from our own group, where NOD2 did not influence the perioperative course after ICR [2], However, there are studies published in the literature that showed an influence of the underlying germline mutation on perioperative outcome [11, 33, 34].

Concerning disease recurrence after resections, our results suggest that a prolonged ICU stay is a possible risk factor. Major complications alone did not lead to an increased risk for disease recurrence; however, numbers for this subgroup were small. Concerning this point, our results differ to some extent from previous studies, which identified surgical complications as risk factors for disease recurrence [22, 30]. Yet, a prolonged ICU stay due to different reasons suggests that a postoperative delay of a disease-specific medical therapy leads to higher recurrence rates.

Although the results presented identified distinct risk factors for more complications after colonic resections for CD, there are some limitations of this study. The retrospective design and therefore heterogeneity of follow-up data as well as data only from a single centre limit the generalisability of our results. However, the size of the study population allowed valid subgroup analysis leading to a more detailed understanding of perioperative courses in case of colonic resections for Crohn’s colitis.

Although results of the presented study are to some extent limited by the size of subgroups, we believe that our results clearly show that colonic resections for CD are a challenging situation in surgery. Higher rates for morbidity after colonic resections than after ICR and higher rates for complications after distal resections indicate that a severe phenotype in combination with a complex surgical procedure is a relevant risk factor for a complicated perioperative course. Prolonged ICU stays were associated with higher rates of recurrence, indicating that a possible delay of prophylactic medical treatment adds to this trend.