Utility of endoscopic diagnosis for postoperative small-bowel lesions in patients with Crohn’s disease at double-balloon endoscopy

ABSTRACT

Double-balloon endoscopy (DBE) has enabled precise diagnosis and endoscopic intervention deep within the small bowel. In this study, we determine the factor related to the risk of endoscopic and clinical recurrences in the diagnosis of postoperative lesions including anastomosis for the patients with Crohn’s disease. Forty-eight patients (40 men and 8 women) had undergone small bowel resection previously and anastomotic sites were evaluated by Rutgeerts’ endoscopic scoring. The factors related to endoscopic and clinical recurrences at anastomosed sites were investigated. The analyzed items included the disease type, anastomosis procedure, frequency of surgery, time to endoscopy after surgery, the presence or absence of treatment with 5-aminosalicylic acid (5-ASA), immunomodulators, steroids, maintenance administration of infliximab, and an elemental diet that required the ingestion of 900 kcal or more per day. Outcome of the anastomosed lesions was analyzed in the groups treated with and without postoperative anti-TNFα antibody including infliximab and adalimumab. DBE was performed 133 times, and 168 anastomosed lesions were observed for enrolled patients. Univariate analysis showed that time to DBE after surgery of 1.5-year or longer and the absence of 5-ASA administration were found to be significant factors leading to both endoscopic and clinical recurrences. The results of Kaplan-Meier estimate and the log rank test demonstrated that the clinical recurrence was avoided more often in the anti-TNFα antibody-treated group compared with the non-treated group. In conclusion, DBE was useful for accurate diagnosis of small-bowel lesions after surgery. Anti-TNFα antibody may help to decrease the postoperative recurrence rate of Crohn’s disease.

INTRODUCTION

Crohn’s disease is a chronic inflammatory disease that manifests throughout the full-thickness of the gastrointestinal layer. Early diagnosis is difficult in many cases, and small-bowel lesions are often accompanied by fistula and stenosis on the first examination and require surgery.^{1, 2)} The reoperation rate is high, and internal therapy, based on evaluation of the small-bowel lesions and endoscopic treatment of the stenosis of the small intestine, may be important to avoid surgery.³⁾ Once healing of the intestinal mucosa has been achieved, the intestinal condition tends to be maintained thereafter in many reported cases.^{4, 5)} The effects of biological agents and immunomodulators in the treatment of Crohn’s disease have been demonstrated, and a high therapeutic efficacy can be expected with multiple drug administrations when the pathology is accurately evaluated, even for intractable cases.⁶⁾ Double-balloon endoscopy (DBE) has enabled precise diagnosis and endoscopic intervention deep within the small bowel.^{7, 8)} Using DBE, endoscopic findings of Crohn’s disease can be observed closely, facilitating understanding of the lesions. DBE also enables close observation of the anastomosed sites after surgery for Crohn’s disease and after endoscopic balloon dilatation of the stenotic lesions.⁹⁾ The objective of this study was to retrospectively review patients who underwent evaluation of the anastomosed sites of the small bowel using DBE after surgery, and to elucidate the characteristics and factors involved in recurrence at the anastomosed sites.

PATIENTS AND METHODS

The subjects were Crohn’s disease patients who underwent DBE assessment of the small bowel mucosa at the anastomosed sites following surgery at our hospital. DBE was performed as reported previously,^{10, 11)} and the findings were reviewed in the DBE database of our hospital, including endoscopic images, and medical records. The background demographics of the patients were also investigated. The condition of the anastomosed lesion site was evaluated in 5 steps, Grades 0–4, using the endoscopic scoring reported by Rutgeerts et al.,¹²⁾ and the following 2 items were investigated: Of the anastomosed lesions classified, those graded 2, 3, and 4 were regarded as endoscopic recurrence, and recurrence-related factors were investigated using univariate analysis. Of the anastomosed lesions classified, those graded 0, 1, 2, and 3 were regarded as clinical remission and the grade 4 lesions were regarded as clinical recurrence. These recurrence-related factors were investigated using univariate analysis.

The analyzed items included the disease type, anastomosis procedure, frequency of surgery, time to endoscopy after surgery, the presence or absence of treatment with 5-aminosalicylic acid (5-ASA), immunomodulators, steroids, maintenance administration of infliximab, and an elemental diet that required the ingestion of 900 kcal or more per day. Since the efficacy of anti-TNFα antibody has been reported recently,¹³⁾ the outcome of the anastomosed lesions was analyzed between the groups that were treated with and without postoperative anti-TNFα antibody.

RESULTS

Data from forty-eight patients at our hospital were reviewed (Table 1). At the time of the first admission to our hospital, the mean age was 37.4 years and the mean duration of illness was 9.3 years. There was a greater number of male patients, and the disease type was small bowel in 32 and small and large bowel in 16 patients, showing that there were more patients with the small bowel type. The mean number of surgeries was 1.4 times. The disease was symptomatic at the time of the first DBE in 31 patients, including abdominal pain and abdominal fullness, and remained asymptomatic in 17 patients. DBE was performed 133 times, and 168 anastomosed lesions were observed. The conditions of the anastomosed sites were classified according to the endoscopic score reported by Rutgeerts et al. (Figure 1).

Table 1.

Characteristics of patients of whom anastomotic sites was evaluated by double-balloon endoscopy

Number of patients	48
Gender (male/female)	40 / 8
Age (y.o., mean±S.D.)	37.4±10.5
Disease duration (mean±S.D.)	9.3±6.2 years
Disease location (Ileal/Iliocolonic)	32 / 16
Post surgical history (times, mean±S.D.)	1.4±0.7

Fig. 1.

Rutgeerts’ scores of 168 anastomotic sites evaluated by DBE

The factors related to endoscopic recurrence at anastomosed sites were investigated. A time to DBE after surgery of 1.5-year or longer and the absence of 5-ASA administration were found to be significant factors leading to endoscopic recurrence (Table 2).

Table 2.

Factors for affecting endoscopic recurrence (Rutgeerts score ≦1 vs. ≧2)

On analysis of factors leading to clinical recurrence, similar to endoscopic recurrence, a duration to DBE of 1.5-year or longer after surgery and the absence of 5-ASA administration were found to be significant (Table 3).

Table 3.

Factors for affecting Clinical recurrence (Rutgeerts score ≦3 vs.4)

The 48 postoperative patients were divided into two groups, with and without administration of anti-TNFα antibody, which were comprised of 22 and 26 patients, respectively. The grade 4 outcomes based on the classification of Rutgeerts et al. were analyzed based upon these 2 treatment groups. The anti-TNFα antibodies were infliximab in 21 patients and adalimumab in 6 patients (5 patients overlapped). They included administration with irregular periods and on demand. The outcomes during the follow-up period (median duration: 51 months) were analyzed using the Kaplan-Meier estimate and the log rank test. The conditions leading to clinical recurrence were avoided more often in the anti-TNFα antibody-treated group compared with the non-treated group (Figure 2).

Fig. 2.

Long-term outcome with or without anti-TNFα antibody (Follow-up Median: 51 months, Range: 5-194 months)

DISCUSSION

Crohn’s disease patients frequently undergo intestinal resection, and surgery is performed for stenotic lesions in many cases. To avoid re-surgery, we propose the periodic evaluation of anastomosed sites and current lesions with endoscopy. Based upon our investigation of the 48 postoperative patients with Crohn’s disease, whose course was followed using DBE at our department, 5-ASA may be effective as a base therapeutic drug, and it may be important to endoscopically evaluate anastomosed sites to determine the therapeutic effect using DBE within 1.5 years after surgery. As Figure 2 showed, the anti-TNFα antibodies were effective for postoperative patients to avoid small bowel stenosis, though the analysis for each lesion did not have same results (Table 2, 3). Ulcerative lesions were observed at most of the anastomosed sites in the group not treated with 5-ASA. Ulcer of the anastomosed region can develop due to the state of Crohn’s disease or can be induced by mild ischemia following anastomosis, and 5-ASA was judged as effective for both conditions. If the anastomosed region has not been observed for a long time after surgery, the therapeutic strategy will be investigated based on symptoms. However, when symptoms become evident, the condition has already progressed to grade 4 of the classification established by Rutgeerts et al. in many cases. Early diagnosis of recurrence at the anastomosed region by endoscopy early after surgery can lead to the prevention of later reoperation. In addition, maintenance administration of anti-TNFα antibody after surgery may be effective in maintaining remission of the anastomosed lesion and preventing stenosis.¹⁴⁾ Improvement of postoperative treatment is essential for patients who have previously undergone surgery, because clinical activity may be or may have been high, however, the patients themselves may not consider it necessary due to the absence of symptoms. In such cases, the necessity of increasing treatment could be explained by showing them the endoscopic lesions.¹⁵⁾

We adopted the classification established by Rutgeerts et al. for our evaluation of the anastomosed regions. However, this scoring system is limited to the evaluation of anastomosed sites and their surroundings, which is not appropriate for evaluation of the entire small intestine after surgery. Indeed, in many cases, the ulcer tends to be limited to the anastomosed region even while the other intestinal region is in remission after ileocecal resection. However, the primary lesion may be present in regions other than the anastomosed region in patients with high disease activity.^{16, 17)} The establishment of a scoring system capable of evaluating the entire small intestine after surgery is anticipated. In conclusion, DBE was thought to be useful for the accurate diagnosis of small-bowel lesions after surgery.

Conflict of Interest

None declared

Abbreviations

DBE

double-balloon endoscopy

5-ASA

5-aminosalicylic acid