Introduction

In patients with refractory constipation, subtotal colectomy with ileorectal anastomosis (SC-IRA) is considered when normal defecatory function and colonic inertia are confirmed, but the outcome is variable.

Aims & Methods

To compare the outcome of quality of life, symptoms, and colorectal physiology measures in medically refractory constipation patients, who were treated conservatively or by SC-IRA.
We contacted 126 refractory constipation patients, who underwent a colonic transit time test, an anorectal manometry (ARM) with balloon expulsion test (BET), and high-resolution colonic manometry (HRCM), for an extensive follow-up survey. This survey includes the Patient Assessment of Constipation quality of life (PACqol) (primary endpoint), and symptoms (PACsym) (secondary endpoint), depression (PHQ9), general anxiety (GAD7) and gastrointestinal specific anxiety (VSI). Colonic inertia was defined as reduced or absent contractions on HRCM after a meal or intracolonic bisacodyl administration. Co-variables were colonic transit time, and ARM with BET baseline results. Results are presented as mean ± standard error of the mean.

Results

We divided 71 respondents into 3 groups based on treatment after HRCM: conservative (n=36), SC-IRA with (n=9), and without (n=26) colonic inertia. The average transit time of the participants (3% men, 45±1.7 years) was 113±3.7 h and was higher in the inertia group compared to the 2 other groups (p=0.001). The 3 treatment groups did not differ in terms of balloon expulsion ability (p=0.80) and rectal sensitivity based on ARM (p=0.62). Follow-up data (n=66) were retrieved on average 4 years (range 1-7) after HRCM and 3 years (range 0-6) after SC-IRA (Table). Both surgical groups had a better (i.e. lower) PACqol satisfaction score than the conservative (both p<0.001). The surgical group without inertia had better outcomes compared to the conservative for general quality of life (p=0.002) and specifically physical discomfort (p=0.02) and worries/concerns (p=0.002). Psychosocial discomfort was lower in the surgical group without colonic inertia compared to those with colonic inertia (p=0.04). No differences were found between the treatment groups for PACsym average (p=0.25) and its subscales of abdominal (p=0.4), rectal (p=0.6), and stool scores (p=0.06), as well as for depression scores (p=0.30). In the surgical group without inertia, the GAD7 score was lower compared to the conservative (p=0.025), while VSI score was lower compared to the inertia group (p=0.046). Overall, depression, GAD, and VSI were correlated with PACqol satisfaction outcomes (r=0.35/p=0.005, r=0.33/p=0.008, and r=0.29/p=0.02 respectively).

Conclusion

On average 4 years after detailed investigation for severe refractory constipation, PACqol satisfaction with stool pattern was higher in those referred for subtotal colectomy, regardless of colonic inertia status, compared to those treated conservatively.

References

Sperber A.D et al. Gastroenterology 2021.
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Corsetti M et al. Gut 2016.
Frank L. et al. Scand J Gastroenterol 1999.
Kocalevent R.D et al. BMC Psychiatry 2013.
Spitzer R.L et al. Arch Intern Med 2006.
Labus J.S et al.- Aliment Pharmacol Ther 2004

Introduction

High-resolution colonic manometry (HRCM) is the gold standard for measuring colonic contractility and guiding decisions for subtotal colectomy in refractory slow-transit constipation (STC). However, it is only available in a handful of centers worldwide. Body surface colonic mapping (BSCM) is a recently validated technology that allows for easy-to-apply and non-invasive transcutaneous evaluation of pre- and post-prandial colonic motility, and has shown strong correlation with HRCM.

Aims & Methods

We sought to evaluate pre- and post-prandial colonic activity using BSCM in patients with refractory STC and correlate with real-time symptoms.
We applied BSCM to refractory chronic constipation patients while undergoing standard diagnostic HRCM. After bowel prep and an overnight fast a HRCM catheter (36 sensors, 3 cm spacing) was advanced and clipped to the caecum. Two BSCM electrode arrays (each 8x8 sensors, 2 cm spacing, Alimetry) were placed on the abdomen after skin prep. Simultaneous HRCM and BSCM recordings were obtained during a 1-hour fasting period, 1 hour after a standardized low-fat meal, and 1 hour after luminally applied 10 mg of bisacodyl. BSCM electrical recordings were band-pass filtered to isolate colonic cyclic motor patterns (CMPs) of 4-10 cycles per minute. The BSCM motility index (MI) was computed from the global continuous wavelet transform spectrum and compared to a real-time symptom score (1-10 scale). Meal response was quantified based on the fasted-fed ratio (FFR) and response time (RT), a marked rise in MI relative to mealtime. Symptoms were recorded for 15 min. during 3,5h.

Results

A total of 9 patients with refractory STC (mean age 45, range 27-60, 22% male) were enrolled. BSCM MI correlated with bloating in 6 subjects, whereof strongly in 2 subjects (R= 0.53 and 0.74). Abdominal discomfort was even correlated to the BSCM MI in 8 subjects, whereof strongly in 2 (R0.74 and 0.79). Flatulence was only reported by 6 subjects and correlated to the BCSM MI in 4 of them, of which 2 strongly (Rs=0.67). While the desire to defecate was correlated with BSCM MI in 6 subjects, the urge to defecate was in 5. However, in both symptoms, there was a strong correlation in 3 subjects (R between 0.69-0.85). These symptoms were mainly provoked by the administration of bisacodyl, followed by strong colonic contractions. Lastly, BSCM MI correlated well with stomach ache symptoms in 6 subjects, of which 2 strongly (R=0.74 and 0.84). Overall symptom burden was strongly correlated with BSCM MI in 3 subjects (R between 0.61-0.8). One subject had clear increases in symptoms, while the colonic activity was low, whereas another subject had an almost perfect correlation between the two. The other subjects had an overall average correlation between symptoms and colonic motility.

Conclusion

BSCM is an easy-to-apply, painless, non-invasive tool that has the potential to elucidate underlying mechanisms driving symptoms in patients with refractory STC. Relating colonic motility to symptoms could aid in developing a more personalized approach to manage these patients' clinical treatment pathway

Introduction

Although irritable bowel syndrome (IBS) is defined as a motility disorder, there is a lack of studies assessing colonic motility in these patients and linking it to symptoms. A recent FODMAP (Fermentable Oligo-, Di-, Monosaccharides, and Polyols) reintroduction study showed that fructans and mannitol triggered IBS symptoms in the majority of patients, while fructose did not, but the mechanism is unclear. Therefore, we set up a study investigating how these FODMAPs trigger colonic motor patterns in healthy volunteers (HV).

Aims & Methods

HV were included in a randomized, double-blind, 3-way crossover study where a 200 mL solution of either fructose, fructans, or mannitol was administered during three study visits, each separated by ≥ 2 weeks of wash-out. Participants followed a low-FODMAP and low-fiber diet for 3 days before each study visit. On the study day, they received a 250mL tap water enema for HRCM catheter placement (36-sensor solid-state) via colonoscopy. After recovery of 1h, colonic pressure waves (PWs) were measured in a fasted state (1h), after a 20-min FODMAP infusion (2h), and after a standardized meal (1h). The number and propagation direction of short PWs (3 sensors), long PWs (≥4 sensors), cyclic PWs, and high-amplitude propagating (retrograde) contractions (HA(R)PCs) were analyzed.

Results

A total of 15 study visits from five HV (40%men, 38±8 years, BMI 23.7±1.6 kg/m²) who finished the full protocol were analyzed. Although none of the motor patterns occurred more frequently with one of the FODMAPs in the fasted state, during FODMAP infusion, 1h post-infusion and postprandially, the short anterograde PWs occurred more frequently in the 2h post-infusion period with fructans compared to fructose and mannitol (p=0.03). Additionally, long synchronous PWs occurred more frequently 1h post-infusion with fructans compared to the fasted state (p=0.01) and there was a trend toward a higher occurrence of long synchronous PWs (p=0.054) and cyclic retrograde PWs (p=0.06) with mannitol

Conclusion

At the current number of healthy volunteers finalizing all 3 visits, fructans and to a lesser extent mannitol but not fructose intracolonic infusions are associated with increased occurrence of synchronous and anterograde colonic motor patterns. Triggering of colonic motor patterns may contribute to symptom triggering by these FODMAPs in IBS.

Introduction

Irritable bowel syndrome (IBS) pathophysiology is multifactorial, with fermentable, oligo, di- and mono-saccharides and polyols (FODMAP) playing a role in symptom induction, presumably through osmotic effects and rapid colonic fermentation. While dietary studies assessed effects on symptoms, few have investigated the direct impact on colonic motility.

Aims & Methods

Using high-resolution colonic manometry (HRCM), we examined the effects of intracolonic fructose, fructans (fructo-oligosaccharides), or mannitol infusion on colonic motility in healthy volunteers (HV).
A double-blind three-way crossover study was conducted in 15 HVs, with a ≥ 2-week wash-out period between visits. After three days of a low FODMAP and low fiber diet, subjects came fasted to the hospital's endoscopy unit. They received a 250 mL water enema before advancing a 36-sensor solid state HRCM catheter with perfusion lumen into the ascending colon via colonoscopy under conscious sedation. After a 1 h recovery period, colonic pressures were recorded 1 h in the fasted state, for 20 min during infusion of FODMAP in the ascending colon (200 mL 290 mOsm/kg fructose, fructans, or mannitol), 2 h post-infusion, and 1 h postprandially after a standardized low-calorie meal. Colonic motor patterns were manually identified and compared between the three FODMAPs, with long ones ≥12 cm and high amplitude ones with at least 3 sensors ≥100 mmHg. Gastrointestinal symptoms were recorded every 15 minutes during the 4.5 h measurement. Results are presented as median with minimum and maximum ranges.

Results

Fifteen HV, 40% male (mean age 32 years (range 19-64 y), mean BMI 22.6 kg/m² (range 19.6-33.1)), completed the three study visits. Post FODMAP infusion, a significant difference in long anterograde patterns (p=0.04) was detected (Table). Postprandially, long synchronous (p=0.001) and long anterograde (LA) (p=0.0008) were more frequently observed with fructans, while mannitol tended to induce long retrograde patterns (p=0.07). Many of the long anterograde patterns were pan-colonic interrupted pressurizations (IP; previously described as related to gas transit; Leibbrandt J Clin Med 2023), and these were significantly more frequent after fructans infusion (p=0.004). High-amplitude retrograde-propagating contractions occurred 36 times in five HV: 50% after mannitol, 25% after fructans, and 25% after fructose infusion. There was no significant difference in gastrointestinal symptoms between the three FODMAPs, although flatulence and abdominal cramps were slightly increased after infusion of fructans.

Conclusion

Fructans and mannitol alter colonic motility patterns in distinct ways. Upon fructan infusion, there is a higher frequency of anterograde and synchronous activity, including interrupted pressurizations, which are suggested to be linked to gas transit. However, the frequency of these motor patterns was not altered by mannitol. These responses to different FODMAPs may contribute to symptom generation in IBS.

References

Van den Houte et al. Gastroenterology 2024
Leibbrandt J et al. Clin Med 2023

Introduction

Opioid-induced constipation (OIC) is a highly prevalent condition among patients treated with opioids for chronic pain. Although constipation and other gastrointestinal side effects can present in 40-90% of opioid users, their effects on colonic motor function and their reversal by opioid antagonists are poorly understood.

Aims & Methods

Our aim was to evaluate the effects of opioids and the reversal effects of a peripheral-acting mu-opioid receptor antagonist (PAMORA) on colonic motor patterns in healthy volunteers (HV), using colonic high-resolution colonic manometry.
We invited 15 healthy volunteers for our randomized, placebo-controlled, double-blind crossover study. The combination of naloxegol/placebo, placebo/codeine, or naloxegol/codeine was administered during three study visits, each separated by at least 1 week of wash-out. Participants underwent a colonoscopy after a half dose of standard PEG preparation for colonic manometry catheter (40-sensor high-resolution manometry catheter 2.5 cm spacing, Laborie, Mississauga, Canada with attached perfusion catheter) placement. Colonic pressure waves (PWs) were evaluated during sleep (1h), in the fasted state (1h), after a standardized bread meal (645 kcal) (2h), and after intraluminal administration of 10 mg bisacodyl (1h). We analyzed the number and direction of propagation of short PWs (over 3-4 sensors), long PWs (>4 sensors), and high-amplitude propagating contractions (HAPCs; long PWs with an amplitude of ≥100 mmHg for at least 1 sensor and 2 sensors of ≥90 mmHg). Upon awakening, participants received 25 mg of naloxegol or matching placebo. In addition, placebo or 60 mg codeine was administered orally, followed by another intake of half this dose one-hour post-prandial. Statistical analyses used a Friedman test and corrected for multiple testing.

Results

Fifteen HV (6 men/9 women, 31.9±3.6 years) finalized all three study visits; one participant was omitted from the analysis because of a missing trace. Both short and long synchronous PWs did not occur statistically significantly more or less in one of the 3 conditions, for all time periods. The same result was found for the antegrade PWs in all time periods. Postprandially, long retrograde PWs occurred statistically significantly less often with naloxegol/placebo compared to placebo/codeine (p=0.04). Additionally, short retrograde PWs occurred less often with naloxegol/placebo than with placebo/codeine (p=0.03). Post bisacodyl administration, both short and long retrograde PWs occurred more often with placebo/codeine, and HAPCs occurred less compared to both naloxegol conditions (Table).

Conclusion

Codeine administration enhances retrograde contractions and inhibits high-amplitude propagating contractions after intraluminal bisacodyl administration in healthy volunteers and these effects are reversed by the PAMORA naloxegol. These observations enhance our understanding of the mechanisms underlying OIC and its treatment with naloxegol.

Introduction

Dyssynergic defecation (DD) is identified in approximately 30% of patients presenting with chronic constipation. Patients with DD usually poorly responded to standard laxative and biofeedback can be offered as the specific treatment. The diagnostic of DD relies on physiological tests including anorectal manometry (ARM) or defecography, which is not universally accessible. As there are lack of single predictive symptom for DD, hence, we aimed to establish a diagnostic score to help with DD diagnosis.

Aims & Methods

This is a retrospective study conducted at Siriraj Hospital. Derivation cohort included 402 refractory constipation patients who were referred to our center for ARM from 2017-2023. While validation cohort of 100 patients were recruited during 2014-2016. Clinical characteristics and results of physiological tests [ARM, balloon expulsion test (BET), and colonic transit time (CTT)] were collected. The interpretation of ARM was conducted in accordance with the London classification. Univariable and multivariable logistic regression analyses were utilized and indicative features of DD were identified. The scoring system was formulated from beta-coefficients and simplified into an integer-point format. The diagnostic performance of this score was then assessed using both cohorts.

Results

The derivation cohort had DD prevalence of 52.49%. 82.09% of this cohort were female and the average age of 52.39 years. Logistic regression analysis identified significant associations between DD and the following clinical characters: duration of symptoms less than two years (OR 1.88; 95% CI=1.02-3.49), had three or more bowel movements per week (OR 4.67; 95% CI=2.47-8.86), straining (OR 7.76; 95% CI=3.57-16.90), sensation of incomplete evacuation (OR 1.95; 95% CI=1.02-3.73), sensation of anorectal blockage (OR 3.71; 95% CI=1.75-7.88), and the use of manual maneuvers to facilitate defecation (OR 2.55; 95% CI=1.37-4.78). An 11-point diagnostic scoring system was developed: 3 points are assigned for straining during defecation; 2 points each for frequent bowel movements, the sensation of anorectal obstruction, and the use of manual maneuvers; 1 point each for a symptom duration of less than two years and the sensation of incomplete evacuation. The diagnostic performance of the score was robust, with an area under the receiver operating characteristic curve (AUROC) of 0.91 (95% CI, 0.88–0.93) in the derivation cohort and 0.88 (95% CI, 0.81–0.95) in the validation cohort. The optimal cutoff was determined to be ≥ 5 points, resulting in a sensitivity of 93.4% (95% CI = 89.1-96.3), a specificity of 72.8% (95% CI = 65.9-79.0), a positive predictive value (PPV) of 79.1% (95% CI = 73.5-84.0), and a negative predictive value (NPV) of 90.8% (95% CI = 85.1-94.9). The score also exhibited excellent calibration performance.


Univariable and multivariable analysis of clinical predictors for defecation disorder

Conclusion

We proposed the first diagnostic score for DD diagnosis. As its simplicity and excellent diagnostic performance, this can be served as a practical tool for all physicians to facilitate early identification of DD. Further diagnostic confirmation by standard physiological tests and quicken triaging patients for biofeedback therapy.

References

Carrington EV, Heinrich H, Knowles CH, et al. The international anorectal physiology working group (IAPWG) recommendations: Standardized testing protocol and the London classification for disorders of anorectal function. Neurogastroenterol Motil. 2020 Jan;32(1):e13679.

Disclosure

The authors declare that they have no conflicts of interest

Introduction

Constipation is a common anorectal symptom that causes significant changes in the patients' quality of life. Anorectal manometry (ARM) and magnetic resonance (MR) defecography are important tools in diagnosing disorders associated with constipation, which are mainly structural and/or functional. Pelvic floor dyssynergia is diagnosed in the presence of alterations in 2 of the following: defecation kinetics in ARM, balloon expulsion test (BET) and/or MR defecography.

Aims & Methods

Compare the findings in ARM and MR defecography, in patients with constipation.
Retrospective cohort study including patients who fulfilled the Roma IV criteria for functional constipation, who were submitted to ARM and MR defecography. The London classification was used to describe the findings in ARM, establishing 3 groups of patients: Group 1 with those who had normal anorectal coordination and normal BET, Group 2 had altered anorectal coordination and altered BET, and Group 3 with those who had inconclusive findings: altered anorectal coordination and normal BET or normal anorectal coordination with abnormal BET. The structural alterations considered significant in MR defecography were those described as moderate to severe, which lead to defecation obstruction.

Results

A total of 51 patients were included, most were female (98.0%), with a mean age of 55 ± 12 years. Regarding the ARM findings, 16 patients were in Group 1 (31.4%), 11 in Group 2 (21.6%) and 24 in Group 3 (47.1%). Forty-three patients had alterations in MR defecography (84.3%), with 42 patients having at least one structural alteration and the most common being rectocele (72.5%) and descending perineum syndrome (66.7%). Pelvic floor dyssynergia was diagnosed by MR defecography in 9 patients (17.6%).
In the group of patients with normal anorectal coordination in ARM and normal BET (Group 1: n=16), 14 had significant structural alterations in MR defecography (87.5%) and 2 patients had no alterations (12.5%). In the group of patients with altered anorectal coordination in ARM and altered BET (Group 2: n=11), 8 also had structural alterations in MR defecography (72.7%). In the group of patients with inconclusive findings in ARM (Group 3: n= 24), 20 had structural alterations (83.3%) and 3 patients had pelvic floor dyssynergia diagnosed by MR defecography (12.5%), 2 of whom had both alterations (8.3%). In this group, 3 patients had no alterations in MR defecography (12.5%).
Patients with pelvic floor dyssynergia, with or without structural alterations, had a significantly lower rectoanal pressure differential than those with solely structural alterations (-25.0 ± 27.1 vs 5.7 ± 30.0 mmHg, p=0.004). There were no statistically significant differences in the values of anal pressure at rest and voluntary contraction pressure between patients with pelvic floor dyssynergia and those with solely structural alterations (p=0.350 and p=0.833), as well as in the values of residual anal pressure, intrarectal pressure and percentage of relaxation during defecation (p=0.267, p=0.257 and p=0.348).

Conclusion

Most patients had alterations in MR defecography, regardless of the ARM findings. Therefore, it is important to interpret the results of the ARM in conjunction with an imaging test capable of identifying structural alterations that may condition defecation in patients with functional constipation. In addition, those with pelvic floor dyssynergia, with or without associated structural alterations, had a lower rectoanal pressure differential than those with solely structural alterations.