A comparison of function lumen imaging probe measurements of anal sphincter function in fecal incontinence

The functional lumen imaging probe (FLIP) is a test of anal sphincter distensibility under evaluation by specialist centers. Two measurement protocols termed “stepwise” and “ramp” are used, risking a lack of standardization. This study aims to compare the performance of these protocols to establish if there are differences between them.


| INTRODUC TI ON
Fecal incontinence (FI) affects 8% of the adult population, 1 with anal sphincter dysfunction considered a principal cause. 2,3Highresolution anorectal manometry (HRAM) with a fixed-diameter catheter is the investigation of choice for sphincter dysfunction. 4wever, resistance to distension has been proposed as the main determinant of sphincter function 5 leading to the development of tests of sphincter distensibility. 6e Functional lumen imaging probe (FLIP) [7][8][9] measures distensibility of a sphincter during volume-controlled distension and has demonstrated utility in the investigation of FI. 6,7,10 However, for research between units to be comparable, standardization of physiological measurements is crucial for the development of this technology to continue. 11Two FLIP measurement protocols termed "stepwise" and "ramp" have emerged from different specialist centers risking a lack of standardization.Using the stepwise protocol, authors have reported distensibility measurements at fixed bag volumes in patients with FI, 12 and healthy controls. 10The ramp protocol, while also measuring parameters at the same fixed bag volumes, adds other measurements during opening and closing of the anal canal, which have clinical utility in the investigation of FI. [13][14][15] These measurements at fixed bag volumes have never been compared between protocols meaning different studies cannot be combined or compared.
This study aims to compare the performance of these two protocols in the same patients to establish if differences exist between them.

| Patient recruitment
Patients with FI were identified prospectively and provided written informed consent.FI severity was assessed with the Vaizey score 16 and the impact on quality of life by the Manchester Health Questionnaire. 17tients were excluded if they lacked cognitive capacity, were pregnant, or had a diagnosis of anorectal cancer or inflammatory bowel disease.

| Functional lumen imaging probe
The EndoFLIP™ system (Medtronic®, MN, USA) uses a highly compliant 12 cm bag that fills with a conductive solution to a diameter of 25 mm (EF-325N catheter).Using impedance planimetry, the diameter of the bag is measured at 5 mm intervals over 8 cm.In combination with a pressure transducer, FLIP records diameter and pressure measurements.

| Functional lumen imaging probe measurement protocols
There are two measurement protocols termed "ramp" and "stepwise" which have been highlighted in a recent review (Figure 1). 6th the ramp protocol, the FLIP bag fills at a rate of 40 mL/min to 10 mL twice, then to 20, 30, 40, and 50 mL.Between each filling volume, the bag is emptied.In the stepwise protocol, the bag is filled at the same rate from 0 to 50 mL in increments of 10 mL without deflation between steps.In each protocol, distension to a fixed bag volume is followed by 30 s of iso-volumetric recording of resting parameters before the patient is asked to squeeze for 10 s.The ramp and stepwise protocol last 13 and 7 min respectively unless the measurements are interrupted by the clinician.
Patients underwent measurement with both protocols with the order randomized by a statistician before recruitment.Between measurements, the catheter was removed, and 5 min elapsed.

| Analysis of the functional lumen imaging probe data
Data were analyzed using a customized MATLAB subroutine (R2022a, Mathworks, Natick, MA, USA) described previously. 18Resting measurements were recorded as the averaged bag pressure and minimum diameter over 10 s during the 30-s resting period.During squeeze assessment, the minimum diameter and corresponding maximum bag pressure were recorded.Cross-sectional area (CSA) was calculated from the corresponding diameter measurements.Distensibility index (DI) is calculated as minimum CSA/bag pressure.

| Statistical analysis
Statistical analysis was performed using SPSS Version 29.0 for Mac® (IBM, NY, USA).The mean differences (mean bias) and 95% confidence interval (95% CI) of the differences were calculated.A paired ttest was used, and statistical significance considered at p < 0.05 level.

| Ethical approval
This study received approval from the local research ethics committee (Greater Manchester West, UK, Ref: 19/NW/0633) and was conducted according to the Declaration of Helsinki.

Key points
1.There is no agreed measurement protocol for FLIP assessments of anal sphincter function.
3. The most relevant FLIP parameter and associated measurement protocol requires agreement through consensus.

| RE SULTS
Twenty patients with FI were included (Table 1).In one patient, distension to 50 mL during the ramp measurement was not tolerated.

| Resting assessment
Measurements obtained at bag volumes 30, 40 and 50 mL are presented in Table 2, with the mean bias calculated as stepwise protocol-ramp protocol.Results at 10 and 20 mL bag volumes are not presented as the anal canal remained closed in all patients.No significant differences were seen in measurements of bag pressure between protocols, although there was a trend towards higher bag pressures during stepwise assessment.There was a difference between the minimum diameter measurements at 30 and 40 mL bag volumes in the stepwise protocol, which were on average, 0.55

| Squeeze assessment
The data obtained at 30, 40, and 50 mL bag volume during squeeze is presented in Table 3. Data obtained at 10 and 20 mL is not presented as the anal canal remained closed in all patients.There were no significant differences in squeeze measurements obtained between the ramp or stepwise measurement protocol.

| DISCUSS ION
This study aimed to investigate if there were differences in measurements between the stepwise and ramp FLIP protocols to F I G U R E 1 Two graphs demonstrating the FLIP distension protocols (A: stepwise, B: ramp).At each volume there is a 30 s isovolumetric resting period before resting parameters are measured (R) followed by squeeze parameters (S).Reproduced from O'Connor et al. 6 establish if results from specialist centers could be combined and compared.However, it has demonstrated there are differences at rest with the minimum diameter and DI from the stepwise protocol less than the ramp protocol at 30 and 40 mL bag volumes.At 50 mL there remained a non-significant trend towards reduced minimum diameter and DI in the stepwise protocol.Furthermore, there was a trend towards greater resting bag pressures in the stepwise assessment.There were, however, no differences observed in measurements of squeeze function between the protocols.
Recent work with HRAM had addressed a lack of standardization which made comparisons between institutions impossible. 4,11wever, while it is invariably the EF-325N catheter used in FLIP measurements of the anal sphincter, 19 there is no such agreed measurement protocol with two currently reported in the literature. 6ere is therefore a risk that if this technology becomes more widespread, institutions will adopt different practices hindering the generalizability of their findings.
The stepwise protocol has been used to describe the distensibility of the anal canal at fixed bag volumes.It can differentiate between patients with FI and healthy controls and is proposed as a complementary tool to HRAM. 8,10By contrast, the ramp protocol adds a dynamic assessment of the sphincter complex during inflation and deflation.Various additional parameters can be measured during opening-closing of the anal canal including the yield pressure and pressure-strain elastic modulus which have been used in the investigation of FI. 13,15 The stepwise protocol is faster to perform at approximately 7 min, whilst the ramp protocol lasts approximately 13 min.
The different results at the same bag volumes observed in this study may be a consequence of the unequal loading-unloading (inflation-deflation) process and prolonged measurement time in the ramp protocol.This changes the viscoelastic properties of the anal sphincter through preconditioning 20,21 which can explain the increased diameter and DI measurements observed at rest in the ramp protocol.Additionally, given the length of the FLIP catheter (12 cm), a significant proportion remains in the lower rectum.This may activate the recto-anal inhibitory reflex to different extents between each protocol, which cannot be quantified with the current single bag catheter design.

measured parameter Mean (SD) stepwise Mean (SD) ramp Mean difference (bias) (stepwise-ramp) 95% C I of bias p value*
Patient characteristics.Percentage calculated from females with vaginal deliveries only.A summary of the differences between squeeze measurements obtained at 30 , 40 and 50 mL bag volumes between a ramp and stepwise FLIP measurement protocol.DI, distensibility index, FLIP, functional lumen imaging probe.a Data from 19 patients used for analysis.*Paired t-test, significance at p < 0.05 level.13652982, 2024, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/nmo.14791by Danish Regions North Denmark, Wiley Online Library on [04/06/2024].See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions)on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License a Female only.bPercentagecalculated from parous females only.cAbbreviations:DI, distensibility index; FLIP, functional lumen imaging probe; SD, standard deviation.aData from 19 patients used for analysis.*Paired t-test, significance at p < 0.05 level.Bold indicates significance at p < 0.05 level.13652982,2024, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/nmo.14791by Danish Regions North Denmark, Wiley Online Library on [04/06/2024].See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions)on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License TA B L E 3