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.
Ianelli A. et al. World J Gastroenterol 2007.
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

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

Functional defecation disorders are causes of obstructive defecation due to alteration in the coordination of abdominal contraction and anal relaxation. Four manometric patterns of dyssynergic defecation (DD) have been described, such that in type I and III there is an alteration of anal relaxation with adequate rectal propulsion, and in types II and IV rectal propulsion fails. According to the Rome IV criteria, the diagnosis of DD requires confirmation with two tests of anorectal function, with the most commonly used being high-resolution anorectal manometry (HRAM) and the balloon expulsion test (BET). Within the manometric parameters, the rectoanal gradient (RAG) appears to be the most useful.

Aims & Methods

To evaluate the clinical characteristics of patients according to patterns of DD defecation and to establish the cutoff point of the RAG and relaxation percentage (RP) that allows predicting balloon expulsion or not.
A total of 960 high-resolution anorectal manometries (HRAMs) performed from January 2021 to April 2024 were reviewed, including 337 patients with DD (35%). Prior to performing the HRAM, epidemiological and clinical data of the patients were collected. Although retrospectively reviewed, all data were prospectively collected. HRAM was performed with solid-state catheters (Medtronic). For BET a balloon (Matla Systems S.L) was filled with 50 mL of water was used under conditions of privacy while sitting on a toilet. Values of 60 seconds or less were considered normal.

Results

Included were 337 patients with a mean age of 61.7 ± 13.9 years. Among them, 226 (67.1%) were female. The diagnosis of DD was confirmed with an altered BET in 96 (28.5%) of the patients. In the remaining cases, the diagnosis of DD was inconclusive.
The epidemiological and clinical characteristics are described in table 1. The presence of associated structural causes was observed in all groups: 102 cases (42.7%) in types I-III; and 52 patients (53.6%) in types II-IV. The frequency for rectal hyposensitivity was 47.5%, and it was similar in both groups: 112 cases (46,6%) in types I-III, and in 48 cases (49,5%) in types II-IV.
The Area Under the Curve (AUC) for RAG was 0.738 (95% CI 0.682 - 0.794), identifying a cut-off value for RAG of -34.1 with an estimated sensitivity of 81.3% and specificity of 57.3% (figure 1). The AUC for RP was 0.544 with a cutoff point of 5.5% (95% CI 0.476 - 0.611), demonstrating low sensitivity (62,5%) and specificity (52,7%) (figure 2).

Conclusion

The frequency of DD diagnosed by HRAM is high (35% in our series), being more common in women. The high coexistence of structural causes, which can give a false manometric pattern of DD, is noteworthy. In types II and IV (rectal propulsion disorders), the diagnosis was confirmed by the failure to expel the balloon more frequently than in types I and III. Rectal hyposensitivity is very frequent in these patients. So far, the Rectoanal Gradient (RAG) is the best parameter of HRAM to evaluate DD. A value below -34 mmHg allows reasonably discriminating whether patients will expel the balloon or not.

Disclosure

No conflict of interests

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.