From the organ bath to the whole person: a review of human colonic motility.

Motor function of the colon is essential for health. Our current understanding of the mechanisms that underlie colonic motility are based upon a range of experimental techniques, including molecular biology, single cell studies, recordings from muscle strips, analysis of part or whole organ ex vivo through to in vivo human recordings. For the surgeon involved in the clinical management of colonic conditions this amounts to a formidable volume of material. Here, we synthesize the key findings from these various experimental approaches so that surgeons can be better armed to deal with the complexities of the colon.

The effects of loperamide on excitatory and inhibitory neuromuscular function in the human colon.

BACKGROUND: In most animal species, opioids alter colonic motility via the inhibition of excitatory enteric motor neurons. The mechanisms by which opioids alter human colonic motility are unclear. The aim of this study was to describe the effects of loperamide on neuromuscular function in the human colon. METHODS: Tissue specimens of human colon from 10 patients undergoing an anterior resection were divided into three inter-taenial circular muscle strips. Separate organ baths were used to assess: (1) excitatory transmission (selective blockade of inhibitory transmission: L-NOARG/MRS2179); (2) inhibitory transmission (selective blockade of excitatory transmission: hyoscine hydrobromide); and (3) a control bath (no drug additions). Neuromuscular function was assessed using force transducer recordings and electrical field stimulation (EFS; 20 V, 10 Hz, 0.5 ms, 10 s) prior to and following loperamide and naloxone. KEY RESULTS: In human preparations with L-NOARG/MRS2179, loperamide had no significant effects on isometric contractions. In preparations with hyoscine hydrobromide, loperamide reduced isometric relaxation during EFS (median difference + 0.60 g post-loperamide, Z = -2.35, p = 0.019). CONCLUSIONS AND INFERENCES: Loperamide had no effect on excitatory neuromuscular function in human colonic circular muscle. These findings suggest that loperamide alters colonic function by acting primarily on inhibitory motor neurons, premotor enteric neurons, or via alternative non-opioid receptor pathways.

The human enteric nervous system. Historical and modern advances. Collaboration between science and surgery.

BACKGROUND: There are considerable advantages and opportunities for surgeons and trainee surgeons in conducting a period of research allied with basic scientists. Such clinicians are well placed to define relevant clinical questions, provide human material (tissue, biopsy and blood) and translate the techniques derived in experimental animals to human subjects. METHODS: This small review explores research conducted on the nervous system of the intestines, with an emphasis on the translation of findings from animal to human. RESULTS: This work shows that new techniques of immunohistochemistry and retrograde tracing, developed in animal tissue, have greatly expanded our knowledge of the structure of the human enteric nervous system. CONCLUSIONS: Such findings have sparked therapeutic trials for the treatment of gastrointestinal disorders in patients.

High-resolution impedance manometry characterizes the functional role of distal colonic motility in gas transit.

BACKGROUND: The colonic motor patterns associated with gas transit are poorly understood. This study describes the application of high-resolution impedance manometry (HRiM) in the human colon in vivo to characterize distal colonic motility and gas transit; (a) after a meal and (b) after intraluminal gas insufflation into the sigmoid colon. METHODS: HRiM recordings were performed in 19 healthy volunteers, with sensors positioned from the distal descending colon to the proximal rectum. Protocol 1 (n = 10) compared pressure and impedance prior to and after a meal. Protocol 2 (n = 9) compared pressure and impedance before and after gas insufflation into the sigmoid colon (60 mL total volume). KEY RESULTS: Both the meal and gas insufflation resulted in an increase in the prevalence of the 2-8/minute "cyclic motor pattern" (meal: (t(9) = -6.42, P<0.001); gas insufflation (t(8) = -3.13, P = 0.01)), and an increase in the number of antegrade and retrograde propagating impedance events (meal: Z = -2.80, P = 0.005; gas insufflation Z = -2.67, P = 0.008). Propagating impedance events temporally preceded antegrade and retrograde propagating contractions, representing a column of luminal gas being displaced ahead of a propagating contraction. Three participants reported an urge to pass flatus and/or flatus during the studies. CONCLUSIONS AND INFERENCES: Initiation of the 2-8/minute cyclic motor pattern in the distal colon occurs both following a meal and/or as a localized sensorimotor response to gas. The near-absence of a flatal urge and the temporal association between propagating contractions and gas transit supports the hypothesis that the 2-8/minute cyclic motor pattern acts as a physiological "brake" modulating rectal filling.

Understanding the physiology of human defaecation and disorders of continence and evacuation.

The act of defaecation, although a ubiquitous human experience, requires the coordinated actions of the anorectum and colon, pelvic floor musculature, and the enteric, peripheral and central nervous systems. Defaecation is best appreciated through the description of four phases, which are, temporally and physiologically, reasonably discrete. However, given the complexity of this process, it is unsurprising that disorders of defaecation are both common and problematic; almost everyone will experience constipation at some time in their life and many will develop faecal incontinence. A detailed understanding of the normal physiology of defaecation and continence is critical to inform management of disorders of defaecation. During the past decade, there have been major advances in the investigative tools used to assess colonic and anorectal function. This Review details the current understanding of defaecation and continence. This includes an overview of the relevant anatomy and physiology, a description of the four phases of defaecation, and factors influencing defaecation (demographics, stool frequency/consistency, psychobehavioural factors, posture, circadian rhythm, dietary intake and medications). A summary of the known pathophysiology of defaecation disorders including constipation, faecal incontinence and irritable bowel syndrome is also included, as well as considerations for further research in this field.

The relationships between the results of contemporary tests of anorectal structure and sensorimotor function and the severity of fecal incontinence.

BACKGROUND: Diagnostic investigations for fecal incontinence (FI) assess the structure and sensorimotor function of the anorectum. Investigations include anorectal manometry, anorectal sensory testing, pudendal nerve terminal motor latencies (PNTML), and endoanal sonography. The severity of FI and results of investigations are often discordant and the rate of symptom resolution following treatment remains <40%. High-resolution anorectal manometry (HRAM) and three-dimensional endoanal ultrasound (3D-US) have been introduced during the last decade. This study aims to assess the strength of relationships between contemporary investigation results and FI severity. METHODS: Adults presenting for investigation of FI were assessed using the St Mark's FI severity score (SMIS), HRAM, anorectal sensory testing, PNTML, and 3D-US. KEY RESULTS: 246 patients were included. There were significant relationships between the SMIS and HRAM (resting pressure rs = -0.23, 95% CI = (-0.34, -0.11), P < .001; squeeze pressure (rs  = -0.26, 95% CI = (-0.37, -0.14), P < .001) and 3D-US (anterior EAS length rs = -0.22, 95% CI = (-0.34, -0.09), P = .001). The relationships between SMIS and HRAM had a greater effect size in those with urge-predominant symptoms (resting pressure: rs = -0.40, 95% CI = (-0.57, -0.20), P < .001, squeeze pressure: rs = -0.34, 95% CI = (-0.52, -0.12), P = .003). Overall, the variance in SMIS accounted for by anorectal investigations was 8.6% (R2 = 0.098, adjusted R2 = 0.086, P < .001). CONCLUSIONS AND INFERENCES: Anorectal investigations are not strong predictors of FI severity. These findings may reflect the multifactorial, heterogeneous pathophysiology of FI, the limitations of the SMIS and anorectal investigations, and contributing factors extrinsic to the anorectum.

Distinct patterns of myogenic motor activity identified in isolated human distal colon with high-resolution manometry.

BACKGROUND: Colonic high-resolution manometry (HRM) has been used to reveal discrete, propagating colonic motor patterns. To help determine mechanisms underlying these patterns, we used HRM to record contractile activity in human distal colon ex vivo. METHODS: Surgically excised segments of descending (n = 30) or sigmoid colon (n = 4) were immersed in oxygenated Krebs solution at 36°C (n = 34; 16 female; 67.6 ± 12.4 years; length: 24.7 ± 3.5 cm). Contractility was recorded by HRM catheters. After 30 minutes of baseline recording, 0.3 mM lidocaine and/or 1 mM hexamethonium were applied. Ascending neural pathways were activated by electrical field stimulation (EFS; 10 Hz, 0.5 ms, 50 V, 5-s duration) applied to the anal end before and after drug application. RESULTS: Spontaneous propagating contractions were recorded in all specimens (0.1-1.5 cycles/minute). Most contractions occurred synchronously across all recording sites. In five specimens, rhythmic antegrade contractions propagated across the full length of the preparation. EFS evoked local contractions at the site of stimulation (latency: 5.5 ± 2.4 seconds) with greater amplitude than spontaneous contractions (EFS; 29.3 ± 26.9 vs 12.1 ± 14.8 mm Hg; P = .02). Synchronous or retrograde propagating motor patterns followed EFS; 71% spanned the entire preparation length. Hexamethonium and lidocaine modestly and only temporarily inhibited spontaneous contractions, whereas TTX increased the frequency of contractile activity while inhibiting EFS-evoked contractions. CONCLUSIONS AND INFERENCES: Our study suggests that the propagated contractions recorded in the organ bath have a myogenic origin which can be regulated by neural input. Once activated at a local site, the contractions do not require the propulsion of fecal content to sustain long-distance propagation.

A delayed presentation of traumatic right hemidiaphragm injury repaired via a laparoscopic approach: A case report.

INTRODUCTION: Diaphragmatic injury is a rare clinical entity which presents a diagnostic and therapeutic challenge. It is three times more common following blunt trauma than penetrating trauma and results in larger tears. A high index of suspicion is required to diagnose diaphragmatic injury. A missed diagnosis following acute injury can later result in life-threatening complications. CASE PRESENTATION: We describe the successful management of a right hemidiaphragmatic injury presenting two weeks following blunt thoracoabdominal trauma using a laparoscopic mesh repair. DISCUSSION: Diaphragmatic injury is rare, with right-sided injuries less common due to the buffering effect of the liver. The diagnosis is made within 24 hours of injury in 75% of cases (Haranal and et al., 2018) [1]. In our patient, symptoms of a right-sided diaphragmatic injury manifested two weeks following a motor vehicle collision. A CT scan of the chest and abdomen confirmed the diagnosis. According to DeBlasio, intermittent symptoms of visceral herniation or incorrect x-ray interpretation are the main reasons for a delayed diagnosis (DeBlasio et al., 1994) [2]. Contrary to common practice where thoracotomy is the preferred method for repair in the absence of associated abdominal injuries, we demonstrated that a right-sided diaphragmatic injury can be successfully managed with a laparoscopic mesh repair. CONCLUSION: Traumatic diaphragmatic injury remains a challenge to emergency physicians and trauma surgeons. Clinicians should be aware of the differing clinical presentations, investigations, and management. Surgical repair can be achieved via laparoscopy, thoracoscopy, laparotomy, and/or thoracotomy. In the case of an isolated right-sided diaphragmatic injury, laparoscopic mesh repair should be considered.

Characterization of the colonic response to bisacodyl in children with treatment-refractory constipation.

BACKGROUND: Colonic manometry with intraluminal bisacodyl infusion can be used to assess colonic neuromuscular function in children with treatment-refractory constipation. If bisacodyl does not induce high-amplitude propagating contractions (HAPCs), this can be an indication for surgical intervention. A detailed characterization of the colonic response to intraluminal bisacodyl in children with constipation may help to inform clinical interpretation of colonic manometry studies. METHODS: Studies were performed in five pediatric hospitals. Analysis included identification of HAPCs, reporting HAPCs characteristics, and an area under the curve (AUC) analysis. Comparisons were performed between hospitals, catheter type, placement techniques, and site of bisacodyl infusion. RESULTS: One hundred and sixty-five children were included (median age 10, range 1-17 years; n = 96 girls). One thousand eight hundred and ninety-three HAPCs were identified in 154 children (12.3 ± 8.8 HAPCs per child, 0.32 ± 0.21 HAPCs per min; amplitude 113.6 ± 31.5 mm Hg; velocity 8.6 ± 3.8 mm/s, propagation length 368 ± 175 mm). The mean time to first HAPC following bisacodyl was 553 ± 669 s. Prior to the first HAPC, there was no change in AUC when comparing pre- vs post-bisacodyl (Z = -0.53, P = .60). The majority of HAPCs terminated in a synchronous pressurization in the rectosigmoid. Defecation was associated with HAPCs (χ2 (1)=7.04, P < .01). Site of bisacodyl administration, catheter type, and hospital location did not alter the response. CONCLUSIONS AND INFERENCES: Intraluminal bisacodyl induced HAPCs in 93% of children with treatment-refractory constipation. The bisacodyl response is characterized by ≥1 HAPC within 12 minutes of infusion. The majority of HAPCs terminate in a synchronous pressurization in the rectosigmoid. Optimal clinical management based upon colonic manometry findings is yet to be determined.