Endoscopic balloon dilation size and avoidance of surgery in stricturing Crohn’s disease

Abstract

BACKGROUND

Endoscopic balloon dilation (EBD) is an effective method for treating stricture-related obstruction in Crohn’s disease (CD). We aimed to identify factors predictive of successful avoidance of surgery, including endoscopic features, in patients undergoing balloon dilation.

METHODS

We performed a retrospective review of patients with symptomatic CD-related intestinal strictures undergoing EBD. Clinical, medication use, laboratory, and dilation data, including the minimum and maximum balloon sizes used, and number of balloons used per endoscopic session were collected. Multivariate analysis by Cox proportional hazard regression was used to model future surgical bowel resection.

RESULTS

In a total of 135 subjects undergoing 292 dilations, multivariate modeling demonstrated that failure to achieve a maximum dilation of 14mm or more increased the risk of surgery (HR 2.88, 95%CL 1.10,7.53). While there was no difference in the risk of future surgery between maximum EBD sizes of 14–15mm and 16–18mm, those reaching 16–18mm exhibited a longer interval between subsequent dilations (mean 240±136.7 vs. 456±357.3 days, respectively, p=0.023). Endoscope passage at index dilation was not predictive of future surgery (HR 0.63 95%CL 0.31, 1.26). Adjusting for covariates of EBD size, stricture location and type, a CRP>1.5mg/dL (HR 2.60, 95%CL 1.12, 5.94) and anti-TNF initiation following index EBD (HR 2.39, 95%CL 1.09, 5.25) increased the risk of future surgery.

CONCLUSIONS

While dilation calibers larger than 14–15mm were not more protective against future surgery, those reaching 16–18mm underwent maintenance dilation less frequently. The risk of surgery associated with post-EBD anti-TNF initiation suggests effective therapy is often employed too late in the disease course.

INTRODUCTION

The modern armamentarium of anti-inflammatory therapies for IBD have improved the natural history of Crohn’s disease (CD), especially when employed prior to the development of extensive irreversible intestinal damage. However, stricturing complications represent the cumulative result of ongoing damage and are a major reason for surgery, disability, and reduced quality of life¹. While evidence is mounting that some strictures may be sufficiently responsive to medical management, many eventually cause obstructive symptoms that require surgery^2,3. While surgical resection of strictured intestinal segments are often needed, such surgeries are not curative. Stricturing disease often recurs, and there are no current therapies that reverse existing fibrostenotic disease ⁴. While stricturoplasty and other bowel sparing techniques are being used more frequently, there remains a continued need to find alternatives to surgery whenever possible ⁵.

Endoscopic balloon dilation (EBD) has been shown to durably delay or prevent surgery in patients with stricturing CD⁶. The application of radial force to the fibromuscular components of intestinal strictures stretches and partially fractures the stenosis, relieving obstructive symptoms that otherwise would require surgery⁷. Most patients report immediate improvement in symptoms following EBD. The symptomatic benefits of EBD can be sustained, with the ability to avoid surgery at one, three, and five years in 80%, 57%, and 52%, respectively, of patients based on retrospective series ⁸. Balloon dilation does present a risk of perforation and bleeding. The incidence of these serious adverse events has been reported to be 5.1% per dilation, and up to 8.7% when assessed by patient following EBD ⁹.

While EBD in CD is effective and reasonably safe, key factors predicting the likelihood of successfully avoiding surgery following dilation remain unclear. The ability to pass the endoscope, stricture overall length of less than 4cm, and the absence of ulceration within the stricture channel have been associated with the avoidance of surgery following EBD ^{10, 11}. There is remaining debate as to whether stricture type, anastomotic vs. de novo, smoking status, C-Reactive protein (CRP), or stricture location affect the response to EBD ^12,9. In addition, practitioners vary in both the selection of patients offered EBD, as well as the endoscopic dilation technique itself. To address this knowledge gap, our aim was to determine how clinical, laboratory, and technical endoscopic dilation factors, specifically EBD sizes, were associated with avoidance or delay of surgery.

METHODS

Selection Criteria

This retrospective study was approved by the University of Michigan Institutional Review Board. Adult patients (age >18) with CD who underwent EBD between 2006–2014 at the University of Michigan Health System were identified using electronic medical records. CD diagnosis was determined by an outpatient ICD-9 code of 555.X plus one IBD medication in two separate encounters with confirmation by manual review of medical records¹³. In efforts to maintain some degree of stricture and EBD homogeneity, selection criteria included strictures within reach of a standard colonoscope in the distal ileum, ileocecal region, or colon. Both anastomotic and de novo intestinal strictures were included. Because of variation in the management and symptoms of various stricture types, patients with malignant, pouch-related, anorectal, ostomy-related, duodenal or jejunal, or strictures requiring deep enteroscopy with a balloon-endoscope were excluded from the analysis.

Clinical Data Collection

Electronic medical records were reviewed using a combination of automated data extraction (University of Michigan Data Warehouse Service), information retrieval search engines (EMERSE), and manual chart review¹⁴. Patient demographics, disease phenotype, surgical history, and medication use history at the time of dilation were extracted. Laboratory data closest to and prior to the index EBD was collected and included CRP, albumin, white blood cell (WBC) and platelet (PLT) counts, and hemoglobin (HGB). CT- and MR-enterography studies performed within four months prior to dilation (where available) were reviewed by a single radiologist, blinded to medical records and outcome, with extraction of maximum bowel wall thickness, stricture length, maximum bowel diameter upstream of structuring disease, and disease activity features of mural hyperenhancement and vascularity. When multiple strictures were present, features from stricture associated with either upstream dilation or the greatest bowel wall thickness were selected. Stricture dilation features were extracted from endoscopic records. Stricture type (de novo vs. anastomotic), intestinal location of the stricture, minimum and maximum balloon size used for dilation, and ability to pass the endoscope following dilation were recorded. Maximum balloon dilation sizes were categorized based on quartiles and typical balloon stage sizes of <14mm, 14–15mm, 16–18mm, and >18mm. When multiple strictures were present in the same intestinal segment, the stricture dilated to the smallest maximum caliber was used.

Primary Outcome Assessment

The primary outcome in this study was the occurrence of surgical resection of intestine following EBD. Surgical interventions included bowel resection, diverting ileostomy, and surgical stricturoplasty. Fistulotomies, ostomy revisions, and non-CD related surgeries (e.g. hernia repair, cholecystectomy) were not included. The time (days) from index EBD to surgery was measured in all patients who underwent surgery. Manual chart review, augmented by medical record search engine techniques (EMERSE), was used to capture the small portion of surgical events occurring outside the institution.

Statistical Analysis

All analyses considered a p-value of ≤0.05 as statistically significant, and were conducted using SAS 9.4 (Cary, NC). Demographic, clinical, endoscopic dilation, and imaging features (where available) at the index dilation were compared between patients who avoided or underwent surgery during the follow up period. Bivariate analysis using Cox proportional hazards regression models were used, comparing each individual predictor to the time until surgical intestinal resection. Kaplan-Meier curves of surgery-free survival, stratified by maximum size balloon dilation achieved, were produced using the LifeTable method. Multivariate Cox proportional hazards regression model building utilized a backward variable selection process with forced inclusion of age, gender, and other covariates deemed clinically relevant a priori. Continuous variables were also explored as categorical variables (with and without ordinal features) to provide the best model fit. Analysis of maximum likelihood estimates provided hazard ratios and confidence limits for each parameter within the model.

Ethical Considerations

The study protocol for data collection and storage was reviewed and approved by the University of Michigan Institutional Review Board.

RESULTS

Patient Characteristics

A total of 210 patients with a verified diagnosis of CD underwent endoscopic balloon dilation during the retrospective study period (2006–2014). Of identified subjects, exclusions included 24 patients for pouch-related dilation, 21 for anorectal strictures, 17 for ostomy-outlet dilation, 7 for requiring deep enteroscopy, 5 for proximal tract CD, and 1 patient was excluded for malignancy-related dilation. The remaining 135 patients underwent a total of 292 endoscopic procedures with EBD over a mean follow up time of 41.7 months (range 26.1–81.3 months) among those avoiding surgery. Among all subjects, 38 (28.1%) underwent surgery with a median time to surgery of 14.7 (range 0.0–69.4) months. There was a non-significant trend of those undergoing surgery being younger compared to surgery avoiders (40.7 vs. 45.9 years, p=0.086). Otherwise, there were no significant differences in gender, disease duration, disease location, or history of fistulizing disease between those undergoing and avoiding surgery on bivariate analysis (Table 1). Regardless of whether EBD patients underwent or avoided surgery, most had a history of prior bowel resection before index EBD (72.2% vs. 63.2%, p=0.311). Examining medication use at index dilation, the majority of those undergoing or avoiding surgery were using an anti-TNF agent (50.0% vs. 64.9%, p=0.200) with 13.2% and 26.8% using combination therapy, respectively (p=0.090). A single complication immediately following EBD was reported (0.34% by dilation, 0.74% by patient) with perforation at an ileocolonic de novo stricture dilated to a maximum diameter of 18mm; the patient underwent urgent bowel resection.

Table 1.

Patient Characteristics

	No Surgery	Surgery	p-value
	n=97	n=38
Age, yrs (SD)	45.9 (15.5)	40.7 (14.8)	0.086
Female, n (%)	40 (41.2)	15 (39.4)	0.621
Fistulizing Disease, n (%)	55 (56.7)	25 (65.8)	0.278
Prior Surgery, n (%)	70 (72.2)	24 (63.2)	0.311
Disease Duration, yrs (SD)	19.6 (12.6)	16.7 (12.0)	0.235
Smoking History, n (%)
Never	60 (61.8)	22 (57.9)	ref
Prior	20 (20.6)	11(28.9)	0.419
Active	14 (14.4)	7 (18.4)	0.688
BMI, kg/m2 (SD)	26.4 (7.2)	25.8 (5.4)	0.649
Medication Use, n (%)
Thiopurine	39 (40.2)	15 (39.4)	ref
Methotrexate	10 (10.3)	4 (10.5)	0.752
Anti-TNF	63 (64.9)	19 (50.0)	0.200
Prednisone	5 (5.2)	3 (7.9)	0.334

Stricture Characteristics

Of all strictures, 38.5% were anastomotic and 38.5% were ileocolonic, involving the ileocecal valve or a continuous segment of ileum and colon. There were no significant differences in stricture type (p=0.324) between those undergoing or avoiding surgery on bivariate analysis (Table 2). Stricture location was not associated with the risk of surgery on bivariate analysis (p=0.593). Those failing to achieve a maximum bowel dilation of 14mm or more were at increased risk of surgery (HR 3.53, 95%CL 1.71, 7.29). Compared to dilations less than 14mm, those achieving maximum dilations of 14–15mm (HR 0.31, 95%CL 0.12, 0.76) and 16–18mm (HR 0.268, 95%CL 0.12, 0.63) exhibited a significant reduction in risk of future surgery (Figure 1). There was no incremental reduction of risk for surgery between maximum dilation achieved of 14–15mm compared to 16–18mm (HR 0.88 95%CL 0.33, 2.37). Interestingly, relative to maximum dilations of 14–18mm, those dilated to >18mm were at greater risk of surgery (HR 2.75, 95%CL 1.18, 6.43). Minimal balloon size used for EBD was not associated with the risk of eventual surgery (HR 0.928, 95%CL 0.70, 1.23).

Table 2.

Stricture Characteristics

	No Surgery	Surgery	p-value
Location, n (%)	n=97	n=38
Ileum	26 (26.8)	11 (28.9)	ref
Ileocolonic	38 (39.2)	14 (36.8)	0.547
Colonic	33 (34.0)	13 (34.2)	0.864
Stricture Type, n (%)
De novo	57 (58.8)	26 (70.3)	ref
Anastomotic	40 (41.2)	12 (31.6)	0.324
Traversing Stricture, n (%)
at Index	75 (77.3)	25 (65.8)	0.159
Ever	85 (87.6)	29 (76.3)	0.046
Maximum Dilation, n (%)
<14mm	19 (19.6)	14 (36.8)	ref
14–15mm	30 (31.0)	7 (18.4)	0.010
16–18mm	39 (40.2)	9 (23.7)	0.002
>18mm	9 (9.2)	8 (21.1)	0.572

Figure 1.

Risk of surgery by maximum balloon dilation size achieved.

Unadjusted Kaplan-Meier analysis stratifying patients by maximum balloon dilation size achieved. Patients achieving a maximum dilation of >14mm were less likely to undergo surgery compared to smaller dilation sizes (p=0.014). There was no further reduction of future surgery in those dilated to 16–18mm compared to 14–15mm (p=0.618), however the time between maintenance dilations was longer in those reaching 16–18mm (456±357.3 vs. 240±136.7 days, respectively, p=0.023).

Strictures unable to ever be traversed by a colonoscope across all dilation sessions (21,15.6%) were associated with an increased hazard of surgery (HR 2.15, 95%CL 1.01, 4.54). However, the ability to traverse a stricture at the index dilation did not reduce the risk of future surgery (HR 1.62, 95%CL 0.83, 3.17). In those undergoing surgery, 71.1% underwent one dilation, 23.7% underwent two, and 5.3% underwent three or more dilations prior to surgery with a mean time of 141±344 days from index dilation to surgery.

Of those avoiding surgery, 61.9% achieved maximum dilation at the index dilation, 25.8% required two dilations, and 12.4% required three or more endoscopic procedures to reach maximum dilation achieved. A mean time of 229 days (SD 265) was required to reach maximum dilation achieved among those avoiding surgery. Of those undergoing another dilation before either surgery or end of follow up, those dilated to a maximum of 14–15mm underwent subsequent maintenance dilation sooner than those achieving 16–18mm (mean 240±137 vs. 456±357 days, respectively, p=0.023). On sub-analysis of anastomotic strictures, 12/52 (23.1%) of patients had eventual revision surgery after a median of 388 days (range 14–1290 days) following index dilation. Similar to de novo strictures, anastomotic strictures dilated to 14–18mm compared to <14mm were less likely to require surgical revision (HR 0.10, 95%CL 0.11, 0.83).

Laboratory and Imaging Predictors of Dilation Success

On bivariate analysis, the mean CRP value at index dilation was greater in those undergoing surgery (1.1 mg/dL) compared to those avoiding surgery (0.61 mg/dL, p=0.015). A CRP value above 1.5 mg/dL [occurring in 44 (32.6%) of the entire cohort] was associated with an increased hazard of eventual surgery (HR 2.64, 95%CL 1.28, 5.44, p=0.009). Other laboratory values within three months of index dilation, including hemoglobin, white blood cell count, platelet count, and albumin, did not differ between those undergoing and avoiding surgery (Supplemental table 1). Despite our expectation, only 78 subjects (57.8%) had cross sectional imaging within four months of index dilation. Analysis of partial imaging data demonstrated no significant difference between radiographic features of those undergoing and avoiding surgery. Considering the small sample size, we elected not to impute missing data and partial imaging data was not included in the multivariate analysis.

Multivariate Model for Predicting Dilation Success

Surgical outcomes were modeled using Cox proportional hazard regression, adjusting for potential covariates; the most parsimonious model (based on the Akaike information criterion) is presented (Table 3). On adjusted analysis, a maximum balloon dilation size of 14–18mm was associated with a reduction in the hazard of surgery by over half compared to those reaching less than 14mm (HR 0.31, 95%CL 0.12, 0.79, p=0.014). Presented alternatively, compared to those achieving 14–18mm, a maximum dilation of less than 14mm conferred an increased hazard of surgery (HR 2.88, 95%CL 1.10, 7.53, p=0.030). Again, dilation greater than 18mm was associated with increased risk of surgery compared to a 14–18mm dilation maximum size (HR 4.13, 95%CL 1.45, 11.76). There was no incremental reduction in risk of surgery for those dilated to 16–18mm compared to those only reaching 14–15mm (HR 1.061, 95%CL 0.33, 3.41, p=0.920).

Table 3.

Multivariate Cox regression predicting surgery following endoscopic balloon dilation

Risk Factor	HR	95% CL		p-value
Maximum Balloon Size	Reference <14mm
14–15mm	0.37	0.118	0.856	0.023
16–18mm	0.31	0.203	0.694	0.002
>18mm	1.06	0.389	2.880	0.911
CRP >1.5 mg/dL	2.60	1.120	5.940	0.027
Anti-TNF use at index	3.77	0.590	25.140	0.270
Anti-TNF initiation post-EBD	2.39	1.091	5.250	0.029
De novo vs. Anastomotic	0.97	0.560	1.675	0.292
Stricture Location	Reference Distal or Terminal Ileum
Ileocolonic	0.89	0.383	2.067	0.785
Colon only	0.76	0.371	1.574	0.466

Maximum balloon size achieved is referenced to those achieving a dilation size of less than 14mm. When referencing to achieving 14–18mm dilation, dilations to less than 14mm carry a hazard ratio for surgery of 2.88, 95%CL 1.10, 7.53).

Abbreviations: EBD, endoscopic balloon dilation; CRP, C-Reactive Protein

The initiation of anti-TNF therapy following EBD was associated with an increased hazard of surgery (HR 2.39, 95%CL 1.09, 5.25, p=0.029). Anti-TNF use at the time of dilation exhibited a non-significant trend of increased hazard of surgery (HR 3.77, 95%CL 0.59, 25.14, p=0.270). A CRP of 1.5mg/dL was also associated with an increased hazard of surgery (HR 2.60, 95%CL 1.12, 5.94, p=0.027). While stricture location (p=0.657) and anastomotic vs. de novo stricture type (p=0.292) were not associated with surgical risk, both significantly contributed to model fit. Projected probabilities of future surgery in high risk (anti-TNF use and CRP >1.5mg/dL) and low risk patients (no anti-TNF use and CRP <1.5mg/dL) are stratified by maximum balloon dilation size in Figure 2. Age, gender, smoking, prior surgery or fistulizing disease, immunomodulator use before and after dilation, other laboratory data, and passage of the endoscope at index dilation were not significant and did not meaningfully influence the model.

Figure 2.

Adjusted Cox model for probabilities of avoiding surgery stratified by maximum balloon dilation size, CRP, and anti-TNF exposure.

Elevated CRP levels and the use of anti-TNF in the setting of existing obstructive symptoms prompting stricture balloon dilation were identified as additional risk factors predicting future surgery. Using the multivariate Cox regression model, surgery free survival is projected in high risk (solid lines) and low risk (dash lines) groups, stratified by maximum achieved balloon dilator size for two years following index dilation.

DISCUSSION

While the efficacy and safety of EBD have been described in previous retrospective analyses, best technical practices for EBD remain unclear. This study aids in addressing the knowledge gap of how the balloon size used impacts effectiveness and durability of EBD, specifically in regards to avoiding surgery. We expected an approximate linear reduction in surgery-free survival with increasing maximum balloon diameter. Our finding of 14mm as the threshold needed to avoid surgery was unexpectedly small. However, frequent dilation is impractical and potentially exposes patients to more risk of severe adverse events. The greater interval between maintenance EBD achieved with 16–18mm compared to 14–15mm maximum dilation sizes (456 vs. 240 days, p=0.023) had a similar efficacy without a detectable increase in complications. Paradoxically, we found patients undergoing dilations >18mm to be at increased risk of surgery compared to 14–18mm maximum dilation sizes. Reviewing the clinical history of each patient, 15/17 (88.2%) previously underwent EBD to 16–18mm. Of those undergoing surgery 7/8 had a partial, but short lived, clinical response to 16–18mm EBD and were subsequently dilated to 20mmin efforts to relieve symptoms attributed to obstruction. We hypothesize these patients’ persistent symptoms, resulting in the decision for surgery, may have been less related to mechanical obstruction and instead the result of refractory disease activity.

Overall, these results are in agreement with a recent large pooled analysis in 1463 patients which demonstrated that larger balloon sizes appear associated with lower probabilities of recurrent dilation ¹⁵. In contrast to our findings, Bettenworth and colleagues found only stricture length, not maximum dilation caliber, to be associated with the future risk of surgery. The analysis presented in this study adjusts for anti-TNF use history, inflammatory biomarkers, and did not include proximal gastrointestinal strictures, which may account for the discrepancy with Butterworth and colleagues’ results. In addition, in the Bettenworth study the minimum dilation size reported was 15mm, whereas nearly 25% of dilations in our study were less then 14mm owing to difference in technical EBD practice patterns.

While increasing dilation caliber appears to reduce the probability of future surgery, some endoscopists may hesitate to perform larger dilations due to concerns for increasing risk of complications. Other studies have reported that balloon sizes of 20mm or more are associated with major complications^8,10. In the Bettenworth et al pooled analysis, 11 EBD-related complications were reported in 1463 patients undergoing 3213 individual dilations. Despite using balloon sizes from 15–25mm, there was no association found between dilation caliber and complications ¹⁵. The low adverse event count within our cohort makes meaningful risk assessment difficult. What remains unclear is whether all strictures can tolerate the same degree of dilation in a single episode, or instead if features exist to stratify the dilation capacity of individual stenoses. The presented data and existing literature suggests the potentially the best balance of optimal dilation may be in the 16–20mm range.

We did not find stricture type (anastomotic vs. de novo) associated with surgery-free survival following EBD, which is in agreement with other studies ^8,11,15. We also found no difference between EBD success by stricture location across ileum, ileocolonic, or isolated colonic disease. Thienpont et al found no association between CRP or medical treatment and surgery free survival⁹. In contrast to their findings, we found a CRP of >1.5mg/dL and anti-TNF initiation following dilation to be risk factors for future surgery in the multivariate analysis. Potentially, the adjustment for maximum dilation size achieved, differences in dilation technique, and separation of existing anti-TNF use from initiation of anti-TNF following EBD explain the difference between these results. We found no association between albumin or other laboratory variables with EBD success. In addition, we did not find the ability to pass the endoscope through the stricture at the index dilation to be predictive of future avoidance of surgery. While cautious to draw conclusions regarding the significance of minimal balloon size used, the data also suggests a small initial stricture aperture should not deter providers from considering EBD.

Attempts to halt fibrostenotic disease progression is the goal of medication intensification, which commonly occurs in response to recognition of complicated CD. Our analysis found that use of anti-TNF or combination therapy at the time of dilation use did not reduce the risk of future surgery following EBD. In fact, the initiation of anti-TNF therapy following dilation increased the risk for future surgery in this retrospective cohort. The conditions where anti-TNF therapy is capable of sufficiently treating stricturing disease are unclear. Anti-TNF initiation in newly diagnosed CD has been shown to reduce future surgery¹⁶. Further, in the CREOLE study of 97 patients with symptomatic strictures, bowel resection and endoscopic dilation were able to be avoiding following adalimumab initiation in 64% after 24 weeks and 29% after a median follow up of 4 years ¹⁷. Yet, prior work by our group found that among patients hospitalized for small bowel obstruction due to stricturing CD, anti-TNF use did not reduce the risk of surgery ¹⁸. While the capacity for anti-TNF therapy to help resolve obstructive disease is apparent, our results suggest that too often disease modifying therapy is initiated after the therapeutic window has closed ¹.

Beyond the retrospective study design, which is a limitation of existing EBD studies, there are several other limitations that should be considered when evaluating the results. Most published EBD studies require patients to either be experiencing obstructive symptoms. Yet, unaccounted variation in provider thresholds to perform initial EBD, subsequent EBD, or surgery are influenced by physician experience, patient acceptance, and surgical candidacy, all of which influence the results. Variation in tolerance for mucosal bleeding and balloon resistance experienced during dilation, and the amount of dilation performed in a single session also varied. Endoscopic technical factors, namely dilation size, while uncontrolled, were the variables we intended to examine. Our measurement of more granular technical detail, including stricture location, balloon size, number of balloon stages used during the procedure, time between dilation, and maximum dilation diameter achieved were used to adjust for practice variation.

Another limitation was that a standardized instrument to measure mucosal injury was not employed across all reports. There is conflicting evidence as to whether the degree of mucosal injury is associated with either EBD efficacy or safety^9,12. Most intestinal strictures contain both moderate-to-severe fibrotic and inflammatory changes and thus activity within the stenosis may be unavoidable ¹⁹. We expected to use enterography to objectively assess disease activity at the strictured segment but only half of patients included underwent imaging in reasonable proximity to their dilation. Finally, we elected not to include ostomy and pouch-related strictures in our analysis, principally due to concern that dilation and surgical decision behavior, and the small sample size from a single center, would skew the results. Prior work has shown that pouch and ostomy related strictures are responsive to balloon dilation, though studies have been limited to experienced referral centers ^5,20.

In conclusion, EBD of CD-related intestinal strictures is more likely to prevent surgery if a diameter of at least 14–15mm is achieved compared to stopping at smaller dilations, regardless of the ability to pass the endoscope following dilation. While there was no further reduction in the need for future surgery using larger size dilations, dilations to 16–18mm resulted in a significantly longer interval between maintenance dilations compared to smaller sizes. Anti-TNF therapy was not protective against surgery among those undergoing EBD, likely due to minimal remaining medically-responsive intestinal damage. While we await the advent of anti-fibrotic medical therapy in CD, we will continue to contend with irreversible CD-complications. EBD, in properly selected patients, provides a method to immediately relieve debilitating obstructive symptoms and either avoid or delay surgery. Still, several issues remain surrounding EBD in CD, including the need for better methods to provide a personalized prediction for EBD response and probability of complication. In addition, prospective study of optimal balloon inflation time, frequency of dilations, and number of dilation that can be safely performed at one time in a given stricture are needed. Both enterography-based techniques, as well as novel methods to assess the mechanical properties of intestine including stiffness imaging using MR, ultrasound, and photo-acoustic imaging, may offer additional insight to guide the technical aspect of EBD in CD²¹.

Supplementary Material

Supplementary Material For Review

Supplemental Table 1. Laboratory and Imaging Data