Long-term Efficacy of Endoscopic Balloon Dilatation in Patients with Small bowel Strictures Secondary to Crohn’s Disease

doi:10.21203/rs.3.rs-2441897/v1

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Long-term Efficacy of Endoscopic Balloon Dilatation in Patients with Small bowel Strictures Secondary to Crohn’s Disease

https://doi.org/10.21203/rs.3.rs-2441897/v1

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Purpose Long-term Efficacy of Endoscopic Balloon Dilatation in Patients with Small bowel Strictures Secondary to Crohn’s Disease were poorly understood.

Methods We retrospectively collected and analyzed clinical data of CD patients with small intestinal strictures that underwent EBD treatment at three medical centers.

Results A total of 65 patients were included in the present study. During a median follow-up time of 869 days, the overall cumulative rate of repeat intervention after initial EBD was 35.4% (n = 23), with the majority (73.5%) occurring within 3 months. Only CRP level and diameter of dilatation balloon were found to be independently associated with repeat intervention, with HRs of 1.171 (95% CI: 1.040-1.319, p = 0.009) and 0.084 (95% CI: 0.014-0.508, p = 0.007), respectively. There was a tendency for anastomotic cases to have a lower risk of repeat intervention after initial EBD compared to non-anastomotic cases and ileocecal valve cases (p = 0.052). More importantly, the median intervention-free survival (IFS) of the anastomotic group was 1756.50 days (95% CI: 1588.03-1924.98 days), which was significantly longer than the non-anastomotic group (1093.91 days, 95% CI: 692.21-1495.61 days, p = 0.044) and the ileocecal valve group (1175.59 days, 95% CI: 786.96-1564.23 days, p = 0.029).

Conclusion In CD patients with small intestinal strictures treated with EBD, overall long-term efficacy was promising, while short-term failure and the requirement of repeat intervention occurred in a subset of individuals. Lower CRP levels and larger balloon sizes were found to be associated with a lower risk of repeat intervention.

Endoscopic balloon dilatation

Small bowel strictures

Crohn’s Disease

Crohn’s disease (CD) is an inflammatory bowel disease (IBD) characterized by skip lesions and chronic inflammation that may lead to fibrosis and eventually to stricture or obstruction of the gastrointestinal (GI) tract. CD frequently affects the terminal ileum and right hemicolon, but it can also affect other parts of the small intestine. Due to the lower frequency of CD in small bowels, these patients have been less studied, including their clinical features, treatment, and outcome.

It is now widely acknowledged that because of heterogeneity and complexity of CD patients with strictures or obstructions, their treatment strategies should be individualized. Currently, three main types of treatments are available clinically, namely pharmacotherapy, endoscopic therapy, and surgery.^1,2 However, the efficacy of pharmacotherapy, such as anti-tumor necrosis factor (anti-TNF) antibodies, is currently unclear and needs to be further elucidated.^3–11 Surgery used to be the only effective treatment until endoscopic therapy, typically endoscopic balloon dilatation (EBD) showed satisfactory results in these patients.¹² Compared to surgery, EBD shows its advantages mainly in terms of less cost and trauma, with comparable efficacy in relieving GI tract strictures or obstructions.¹² Nevertheless, a major concern of EBD is the recurrence of the stricture, which eventually requires re-dilatation or surgery. However, the short- and long-term efficacy of EBD in CD patients with small bowel strictures is poorly understood. Most of previous studies have focused on CD patients with strictures in the terminal ileum and colon rather than other parts of the small intestine.^13–15 And many studies included strictures of different causes (primary or anastomotic).^13–16 In addition, only a few studies have investigated risk factors for stricture recurrence or the need for another intervention. Therefore, it is important to clarify the efficacy and risk factors in different subgroups of CD patients with small bowel strictures.

In this study, we retrospectively collected CD patients with small intestinal strictures from three medical centers with the aim of examining the efficacy of EBD in these patients. We studied the cumulative rate of repeat intervention after initial EBD treatment and also investigated risk factors for repeat intervention and long-term efficacy of EBD treatment. We also investigated the efficacy of concurrent pharmacotherapy, such as anti-TNF antibodies.

Ethical considerations

The retrospective study was conducted in accordance with the Declaration of Helsinki and was approved by the ethics committees of the First Affiliated Hospital and the Sixth Affiliated Hospital of Sun Yat-sen University, and the Third Xiangya Hospital of Central South University. Informed consent was waived due to its retrospective nature.

Patients

We reviewed CD patients with symptomatic small bowel strictures from three medical centers, the First Affiliated Hospital and the Sixth Affiliated Hospital of Sun Yat-sen University, and the Third Xiangya Hospital of Central South University between July 2013 and September 2020. The inclusion criteria were: (1) was diagnosed with CD; (2) had small bowel strictures confirmed by imaging examinations; and (3) underwent EBD. Patients were excluded if they met any of the following criteria: (1) had a previous EBD; (2) was diagnosed with postoperative intestinal adhesions; (3) presented with a fistula. Data was obtained from the electronic medical records of all medical centers. The technique of dilation was similar among the three medical centers.

Clinical Variables

Clinical variables were collected and recorded, including gender, age, body mass index (BMI), history of smoking, locations of strictures, upper GI tract involvement, disease behavior, concurrent pharmacotherapy, history of surgery, lab test results (within 7 days before the operation), obstructive symptoms, general condition, degree of abdominal pain, frequency of diarrhea, non-GI tract manifestations, thickening of GI tract, mucosal enhancement, length of stricture, presence of ulceration at the stricture, presence of other lesions at the stricture, diameter of dilatation balloon, times of dilatation, relief of obstructive symptoms within 1 week, and further intervention. CD patients who underwent small bowel resection and developed anastomotic strictures were classified as the anastomotic group, while CD patients who developed non-anastomotic strictures were divided into the non-anastomotic and the ileocecal valve groups based on the location, regardless of the surgery history.

Endpoints and definitions

The primary endpoint of this study was the cumulative rate of repeat intervention after initial EBD. The secondary endpoints were risk factors for repeat intervention after initial EBD and intervention-free survival (IFS). IFS was defined as the time interval from the date of initial EBD to the date of secondary intervention or the date of final follow-up, whichever came first. We also analyzed the efficacy of concurrent pharmacotherapy, such as anti-TNF antibodies in these patients.

Statistical analysis

For comparisons between two groups, Chi-square tests or Fisher’s exact tests were used for categorical variables, while Student’s t-tests were used for continuous variables. For comparisons between multiple groups, Chi-square tests or Fisher’s exact tests were used for categorical variables, while one-way ANOVA analyses were used for continuous variables. Logistic regression analyses were performed to identify risk factors associated with repeat intervention after initial EBD. After univariate analyses, all variables with P values less than 0.10 were considered in subsequent multivariate analyses. Survival analyses were performed by plotting the Kaplan-Meier survival curves in which log-rank tests were used to detect statistically significant differences. All statistical tests were two-tailed and performed using the Statistical Package for the Social Sciences (SPSS) software, version 25.0 (IBM, Armonk, NY).

Clinical characteristics, follow-up, and cumulative rate of repeat intervention after initial EBD in CD patients with small bowel strictures

A total of 65 CD patients from three medical centers were included in the study. The clinical characteristics of the patients were shown in Table 1. Only two of them developed intestinal perforation after EBD treatment. The median follow-up time for all patients was 869 days (range: 1-3075 days). During the follow-up period, the overall cumulative rate of repeat intervention after initial EBD was 35.4% (n = 23). More importantly, 17 of these 23 cases (73.9%) needed a further intervention within 3 months after initial EBD (Figure 1). For the other six patients, repeat intervention happened between 205 to 1601 days after initial EBD (Figure 1). Of the 23 patients with repeat intervention, most (n = 19) underwent repeat EBD, while only four underwent surgery. After a secondary intervention, six patients still needed a third intervention and three of them need a fourth one. Moreover, two patients received a total of six interventions during the follow-up period, indicating resistance to the treatments.

Comparison of clinical characteristics of CD patients with small intestinal strictures based on different locations

According to the locations of the small intestinal strictures, patients were divided into three groups: non-anastomotic (n = 22), ileocecal valve (n = 17), and anastomotic (n = 26). Among these non-anastomotic cases, the number of patients with locations in the duodenum, jejunum and ileum was 13, 2 and 7, respectively. Most clinical characteristics such as gender, age, BMI, history of smoking, disease behavior, concurrent pharmacotherapy, laboratory results, number of obstructive symptoms, general condition, degree of abdominal pain, frequency of diarrhea, number of non-GI tract manifestations, thickening of GI tract, mucosal enhancement, presence of ulceration at the stricture, presence of other lesions at the stricture, diameter of dilatation balloon, times of dilatation, and relief of obstructive symptoms within 1 week did not differ significantly between the three groups (Table 1). A higher proportion of non-anastomotic cases had upper GI tract involvement compared to the other two groups (p = 0.001) (Table 1). Regarding the history of surgery, the anastomotic group had the highest proportion, followed by the ileocecal valve group and then the non-anastomotic group (p < 0.001) (Table 1). More patients in the anastomotic group had a length of stricture ≤ 1 cm compared to the other two groups (p = 0.005) (Table 1). Although the difference in repeat intervention after initial EBD was not statistically significant, the proportion tended to be lower in the anastomotic group (p = 0.059) (Table 1).

Risk factors associated with repeat intervention after initial EBD

We next investigated the risk factors associated with repeat intervention after initial EBD in CD patients with small bowel strictures. We first conducted univariate analyses to screen all collected clinical variables (Table 2). Clinical variables were compared between the non-repeat intervention group and the repeat intervention group. Based on a p value threshold of 0.1, seven clinical variables were significantly different between two groups, which were history of smoking (p = 0.041), anti-TNF antibody (p = 0.009), CRP (p = 0.003), degree of abdominal pain (p = 0.064), location (p = 0.059), length of stricture (p = 0.045), and diameter of dilatation balloon (p = 0.055). We then included these seven variables in multivariate analysis to identify independent risk factors. The result of the multivariate analysis was shown in Table 3. Only CRP and the diameter of dilatation balloon were found to be independently related to repeat intervention, with HRs of 1.171 (95% CI: 1.040-1.319, p = 0.009) and 0.084 (95% CI: 0.014-0.508, p = 0.007), respectively. There was a trend toward lower risk of repeat intervention after initial EBD in anastomotic cases compared to non-anastomotic cases and ileocecal valve cases (p = 0.052).

Comparison of intervention-free survival between different subgroups

To further understand the long-term efficacy of EBD in CD patients with small intestinal strictures, we then calculate the intervention-free survival for all patients. Overall, the median intervention-free survival of all patients was 1175.59 days (95% CI: 786.96-1564.23 days) (Figure 2A). The median IFS in the anastomotic group was 1756.50 days (95% CI: 1588.03-1924.98 days), significantly longer than in the non-anastomotic group (1093.91 days, 95% CI: 692.21-1495.61 days, p = 0.044) and the ileocecal valve group (1175.59 days, 95% CI: 786.96-1564.23 days, p = 0.029) (Figure 2B). In agreement with the result of multivariate analysis, patients with higher CRP levels showed worse IFS, compared with those with lower CRP levels (Figure 2C). In addition, the use of a dilation balloon with a diameter of 18 mm but not < 18 mm improved IFS in CD patients with small bowel strictures (Figure 2D).

In this study, EBD showed promising efficacy with good safety profile in CD patients with small bowel strictures. The cumulative rate of repeat intervention in CD patients was 35.4% over a median follow-up time of 839 days. More importantly, 73.9% of cases requiring further intervention happened within 3 months after initial EBD. The anastomotic group tended to have a lower risk of repeat intervention after initial EBD, compared to the other two groups. Independent risk factors associated with repeat intervention included higher CRP level and smaller balloon size. Anastomotic cases, patients with lower CRP levels, and patients with larger balloon sizes had better intervention-free survivals than their counterparts.

EBD had been reported to have the disadvantage of potential treatment failure, which then requires repeat interventions in CD patients with strictures or obstructions. During a median follow-up time of 839 days, we observed a cumulative rate of 35.4%, which was slightly better than the result reported in a previous meta-analysis study.¹⁷ The difference may be explained by the different study periods, as the meta-analysis included patients treated with EBD between 1991 and 2013.¹⁷ Another potential reason is that the majority (98.6%) of cases in their study were ileal.¹⁷ More importantly, we found that most of treatment failures occurred within 3 months, suggesting only short-term efficacy in these patients, which is quite consistent with previous studies.¹⁷ This result suggests that follow-up after EBD treatment is extremely important, especially within 3 months after the procedure, which can help to assess the efficacy and to detect those patients who need further intervention at an early stage. We also found that a small number of patients required multiple interventions (EBD or surgery) after initial EBD, indicating treatment resistance in some cases. In these patients, further treatment strategies should be developed to improve clinical outcomes. New treatment approaches or combination therapies may be useful for them.

In this study, we found that anastomotic cases had a lower risk of repeat intervention and longer IFS after initial EBD, compared to non-anastomotic cases and ileocecal valve cases. Similarly, several previous studies have shown that anastomotic strictures had better long-term outcomes than de novo strictures.^18,19 However, some studies reported that there was no difference between anastomotic and de novo strictures in terms of procedure success and long-term outcomes.^{14,16,17,20−29} EBD is widely used in anastomotic cases to avoid secondary surgery and more trauma. Our observation that the efficacy of EBD is better in anastomotic cases than in non-anastomotic cases further supports its role in these patients. Surgical resection of previous strictures results in scarring followed by potential secondary strictures. Differently, primary strictures were caused by inflammation and subsequent fibrosis, which also indicated the activity and severity of the disease itself. Hence, primary stricture cases may have more aggressive clinical courses and worse clinical outcomes, regardless of the treatments. In such cases, more aggressive medical interventions, such as surgery or more frequent follow-up after EBD should be considered to improve the long-term survival of these patients.

We also found that high CRP levels predicted a higher risk of repeat intervention, which was consistent with the results of previous studies.^25,30 CRP has been used as an indicator of inflammation, with higher CRP levels implying more severe inflammation and vice versa. In CD, CRP was also used as an indicator of disease activity and severity, which may be directly related to the formation of the strictures or obstructions. In clinical practice, the level of CRP is easily determined by blood testing, which makes it convenient and useful in the prediction of EBD treatment efficacy. Though so, various measurement methods and thresholds are used in different medical centers, which may lead to heterogeneity of its value for efficacy prediction. For example, there were also some studies that failed to find a predictive function of CRP level in CD patients.^6,28,31,32 In our study, we performed logistic regression analysis with CRP level as a continuous variable and used its median as the cut-off value for survival analysis to avoid bias caused by speculation. In conclusion, when CRP level is used as a predictor, appropriate cut-off values and standard measures should be considered.

The size of dilation balloon used for EBD varies in CD patients with small strictures. In our study, we found that a balloon size of 18 mm was associated with a lower risk of repeat intervention and a longer IFS after initial EBD, compared with a balloon size less than 18 mm. Several previous studies have also reported that smaller balloon sizes were associated with poorer efficacy of EBD treatment, although the thresholds were heterogeneous.^{16,20,21,24,25,28,29,33} Others claimed that balloon size failed to predict effect.^32,34−37 Some have found that balloon size was only associated with EBD success but not with long-term outcomes.²² In the present study, averagely smaller balloon sizes (the maximum was 18 mm) were used compared to other studies since the location of dilation was in the small intestine. Despite of that, our finding was similar to those of most previous studies in that balloon size may influence the outcome of EBD treatment. The larger the balloon size, the lower the risk of repeat intervention. However, it should be also noted that inappropriate balloon size in narrow and fragile intestinal tracts may lead to perforation and other complications. In our study, only 2 out of 65 patients developed intestinal perforation after EBD treatment, which indicated successful procedures with proper balloon sizes in most cases. Hence, under the premise of ensuring safety, a larger balloon size should be considered to improve the treatment efficiency of EBD in CD patients with small bowel strictures.

The degree of abdominal pain had a tendency to predict the risk of repeat intervention. The symptom somehow reflected the severity of the strictures or obstructions, which was related to the difficulty and efficacy of EBD treatment. Some previous studies have also claimed that severity of symptoms was related to the success and long-term effect of the EBD in CD patients.^38,39 Surprisingly, the use of anti-TNF antibodies did not improve the clinical outcomes of patients. On the contrary, it tended to increase the risk of repeat intervention, although the result was not statistically significant. Several previous studies have also found similar results.^22,25 However, some studies have come to the opposite conclusion regarding the effect of anti-TNF antibodies on CD patients received EBD.^35,36 It has also been shown that medical therapy did not affect clinical outcomes of CD patients underwent EBD.^6,16,40 The timepoint of use of anti-TNF antibodies in EBD-treated CD patients may have a different impact on short-term success or long-term survival.²⁵ In addition, the duration and dosage of anti-TNF antibodies could be various in patients. Considering the retrospective nature of these studies and our study, the proper administration and potential effect of anti-TNF antibodies, as well as other current medication, should be further investigated in well-designed prospective randomized controlled trials.

This study has some limitations that need to be considered when interpreting the results. This is a retrospective study and there may be some patients with missing or inaccurate medical information. And as we only included CD patients with small bowel but not colon strictures, the sample size was relatively small. Moreover, medical therapies in patients were various in many aspects, including medication, timing, dose, and etc. In this context, it is difficult to draw proper conclusions regarding their effect on CD patients treated with EBD. In summary, further large-scale prospective clinical trials are needed to validate these findings.

In this study, we analyzed clinical data of CD patients with small bowel strictures underwent EBD treatment and found that the long-term outcomes were comparable to previous studies, with a subset of patients requiring multiple repeat interventions. CRP level and balloon size independently predicted the efficacy of the initial EBD, while location, degree of abdominal pain, and use of anti-TNF antibodies may be potential risk factors.

Authors contribution Zelong Liu: data analysis and manuscript drafting; Jiachen Sun, Ning Zhang: endoscopic balloon dilatation performance; Hongsheng Yang, Huixian Lin, Miao Li, Zhongcheng Liu, Mrigul Kurban: data collection; Xiang Gao: manuscript critical revision; Qin Guo: conceptualization, study design, endoscopic balloon dilatation performance and manuscript critical revision. All the authors have approved the final draft submitted.

Funding This study was financially supported in part by National Natural Science Foundation of China (81870382 and 82100544), Guangdong Basic and Applied Basic Research Foundation (2020A1515111102), China Postdoctoral Science Foundation (2021M703743), and National Key Clinical Discipline.

Ethics and consent statement This study has been registered in the Chinese Clinical Trial Registry (No. ChiCTR1900023696). Written informed consent from the participants’ legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.

Conflict of interest The authors declare no competing interests.

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Table 1 Clinical characteristics of CD patients with small intestinal strictures
	Non-anastomotic (n = 22)	Anastomotic (n = 17)	Ileocecal valve (n = 26)	P value
Gender				0.373
Male	19	13	18
Female	3	4	8
Age (Mean ± SD)	31.45 ± 9.11	32.12 ± 6.86	31.81 ± 8.69	0.973
BMI (Mean ± SD)	19.31 ± 2.82	19.20 ± 1.94	19.21 ± 1.95	0.986
History of smoking				0.395
No	20	17	25
Yes	2	0	1
Upper GI tract involvement				0.001*
No	11	15	24
Yes	11	2	2
Behavior				0.227
B2	12	4	14
B2+B3	5	7	3
B2+B3+P	4	3	5
B2+P	1	3	4
Concurrent pharmacotherapy				0.910
No	14	10	15
Yes	8	7	11
Anti-TNF antibody				0.938
No	16	13	20
Yes	6	4	6
Thalidomide				0.290
No	22	15	24
Yes	0	2	2
Azathioprine				0.752
No	20	16	25
Yes	2	1	1
Others				0.952
No	20	15	23
Yes	2	2	3
History of surgery				<0.001*
No	16	0	14
Yes	6	17	12
WBC (Mean ± SD)	6.13 ± 1.93	5.31 ± 2.58	5.82 ± 2.08	0.509
PLT (Mean ± SD)	244.45 ± 78.88	211.18 ± 87.98	281.19 ± 85.32	0.031*
HB (Mean ± SD)	128.41 ± 19.76	125.78 ± 22.35	120.85 ± 25.17	0.507
CRP (Mean ± SD)	4.26 ± 4.68	2.06 ± 3.13	4.96 ± 7.34	0.252
ESR (Mean ± SD)	17.19 ± 16.63	13.76 ± 11.36	19.23 ± 18.28	0.559
ALB (Mean ± SD)	40.43 ± 4.91	39.09 ± 4.74	40.32 ± 6.03	0.696
Na+ (Mean ± SD)	140.17 ± 1.85	139.69 ± 2.62	140.53 ± 2.00	0.456
K+ (Mean ± SD)	3.82 ± 0.22	3.93 ± 0.25	4.05 ± 0.35	0.025*
AST (Mean ± SD)	19.87 ± 5.87	20.74 ± 8.22	19.19 ± 6.52	0.765
ALT (Mean ± SD)	33.50 ± 13.97	37.33 ± 13.12	34.88 ± 13.36	0.679
GGT (Mean ± SD)	23.57 ± 14.70	26.46 ± 21.28	29.57 ± 36.05	0.748
TB (Mean ± SD)	14.53 ± 8.06	16.31 ± 15.32	13.12 ± 5.62	0.578
Number of obstructive symptoms				0.756
0-1	13	8	14
2-3	9	9	12
General condition				0.111
Bad	11	14	17
Good	11	3	9
Degree of abdominal pain				0.753
No	7	4	5
Low	9	6	11
Moderate	3	4	7
High	1	3	3
Frequency of diarrhea				0.800
0	13	10	14
1 times/day	5	4	4
≥ 2 times/day	4	3	8
Number of non-GI tract manifestations				0.353
0	19	15	19
1	3	2	7
Thickening of GI tract				0.054
No	0	2	0
Yes	22	15	26
Mucosal enhancement				0.199
No	1	2	0
Yes	21	15	26
Length of stricture				0.005*
≤ 1 cm	6	13	6
＞1 cm	12	4	16
Presence of ulceration at the stricture				0.699
No	19	14	20
Yes	3	3	6
Presence of other lesions at the stricture				0.576
No	18	12	18
Yes	4	5	8
Diameter of dilatation balloon				0.210
＜18 mm	15	9	15
18 mm	4	8	11
Times of dilatation				0.803
1	19	16	22
2	2	1	3
Relief of obstructive symptoms within 1 week				0.960
No	3	3	4
Yes	18	14	22
Repeat intervention				0.059
No	12	15	15
Yes	10	2	11

CD, Crohn’s disease; SD, standard deviation; BMI, body mass index; GI tract, gastrointestinal tract; TNF, tumor necrosis factor; WBC, white blood cell; PLT, platelet; HB, hemoglobin; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; ALB, albumin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, γ-glutamyl transpeptidase; TB, total bilirubin.

Table 2 Univariate analysis of risk factors for repeat intervention after initial EBD

	Non-repeat intervention (n = 42)	Repeat intervention (n = 23)	P value
Gender			0.544
Male	31	19
Female	11	4
Age (Mean ± SD)	32.14 ± 8.90	31.09 ± 8.45	0.643
BMI (Mean ± SD)	19.23±2.14	19.27±2.46	0.941
History of smoking			0.041*
No	42	20
Yes	0	3
Upper GI tract involvement			0.297
No	34	16
Yes	8	7
Behavior			0.732
B2	21	9
B2+B3	9	6
B2+B3+P	8	4
B2+P	4	4
Concurrent pharmacotherapy			0.138
No	28	11
Yes	14	12
Anti-TNF antibody			0.009*
No	36	13
Yes	6	10
Thalidomide			0.610
No	40	21
Yes	2	2
Azathioprine			1.000
No	39	22
Yes	3	1
Others			0.406
No	36	22
Yes	6	1
History of surgery			0.841
No	19	11
Yes	23	12
WBC (Mean ± SD)	5.61±2.21	6.14±2.06	0.346
PLT (Mean ± SD)	251.64±97.59	248.26±66.54	0.883
HB (Mean ± SD)	124.36±22.64	125.30±23.08	0.874
CRP (Mean ± SD)	2.44±3.79	6.74±7.35	0.003*
ESR (Mean ± SD)	15.50±14.88	20.18±18.09	0.272
ALB (Mean ± SD)	40.41±4.77	39.35±6.20	0.448
Na+ (Mean ± SD)	140.05±2.13	140.45±2.14	0.471
K+ (Mean ± SD)	3.98±0.30	3.88±0.31	0.206
AST (Mean ± SD)	18.90±6.41	21.51±7.09	0.137
ALT (Mean ± SD)	34.43±13.95	36.19±12.48	0.616
GGT (Mean ± SD)	28.60±31.60	23.53±13.76	0.469
TB (Mean ± SD)	14.73±10.59	13.89±7.99	0.743
Number of obstructive symptoms			0.215
0-1	25	10
2-3	17	13
General condition			0.537
Bad	26	16
Good	16	7
Degree of abdominal pain			0.064*
No-Low	30	12
Moderate-High	10	11
Frequency of diarrhea			0.877
0	24	13
1 times/day	9	4
≥ 2 times/day	9	6
Number of non-GI tract manifestations			0.515
0	33	20
1	9	3
Thickening of GI tract			0.536
No	2	0
Yes	40	23
Mucosal enhancement			0.547
No	3	0
Yes	39	23
Location			0.059*
Non-anastomotic	12	10
Anastomotic	15	2
Ileocecal valve	15	11
Length of stricture			0.045*
≤ 1 cm	19	6
> 1 cm	16	16
Presence of ulceration at the stricture			0.241
No	36	17
Yes	6	6
Presence of other lesions at the stricture			0.993
No	31	17
Yes	11	6
Diameter of dilatation balloon			0.055*
< 18 mm	21	18
18 mm	18	5
Times of dilatation			0.660
1	37	20
2	3	3
Relief of obstructive symptoms within 1 week			0.148
No	4	6
Yes	37	17

EBD, endoscopic balloon dilatation; SD, standard deviation; BMI, body mass index; GI tract, gastrointestinal tract; TNF, tumor necrosis factor; WBC, white blood cell; PLT, platelet; HB, hemoglobin; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; ALB, albumin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, γ-glutamyl transpeptidase; TB, total bilirubin.

Table 3 Multivariate analysis of risk factors for repeat intervention after initial EBD

Variables	HR (95% CI)	P value
History of smoking (Yes vs. No)	-	0.999
CRP	1.171 (1.040-1.319)	0.009*
Location
Non-anastomotic	-	0.135
Anastomotic	-	0.052
Ileocecal valve	-	0.196
Degree of abdominal pain (Moderate-High vs. No-Low)	-	0.063
Length of stricture (> 1 cm vs. ≤ 1cm)	-	0.124
Diameter of dilatation balloon (18 mm vs < 18 mm)	0.084 (0.014-0.508)	0.007*
Anti-TNF antibody (Yes vs. No)	-	0.085

EBD, endoscopic balloon dilatation; HR, hazard ratio; CI, confidence interval; CRP, C-reactive protein; TNF, tumor necrosis factor.

No competing interests reported.

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Long-term Efficacy of Endoscopic Balloon Dilatation in Patients with Small bowel Strictures Secondary to Crohn’s Disease

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Abstract

Figures

Introduction

Methods

Ethical considerations

Patients

Clinical Variables

Endpoints and definitions

Statistical analysis

Results

Clinical characteristics, follow-up, and cumulative rate of repeat intervention after initial EBD in CD patients with small bowel strictures

Comparison of clinical characteristics of CD patients with small intestinal strictures based on different locations

Risk factors associated with repeat intervention after initial EBD

Comparison of intervention-free survival between different subgroups

Discussion

Declarations

References

Tables

Additional Declarations

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