High-Resolution Colonic Manometry Pressure Profiles Are Similar in Asymptomatic Diverticulosis and Controls.

BACKGROUND: Elevated colonic pressures and increased colonic activity have been thought to contribute to the pathophysiology of diverticulosis. However, evidence for this has been limited to low-resolution manometry, which is of limited accuracy. AIMS: This study aimed to evaluate the contraction pressures, counts, and distance of propagation recorded by high-resolution colonic manometry in diverticulosis vs control patients. METHODS: High-resolution colonic manometry was used to record descending and sigmoid colon activity pre- and post-meal in patients with established, asymptomatic diverticulosis and in healthy controls. Antegrade and retrograde propagating contractions, distance of propagation (mm), and mean contraction pressures (mmHg) in the descending and sigmoid colon were compared between patients and controls for all isolated propagating contractions, the cyclic motor pattern, and high-amplitude propagating contractions independently. RESULTS: Mean manometry pressures were not different between controls and diverticulosis patients (p > 0.05 for all comparisons). In the descending colon, diverticulosis patients had lower post-meal mean distance of propagation for all propagating contractions [10.8 (SE1.5) mm vs 20.0 (2.0) mm, p = 0.003] and the cyclic motor pattern [6.0 (2.5) mm vs 17.1 (2.8) mm, p = 0.01]. In the sigmoid colon, diverticulosis patients showed lower post-meal mean distance of propagation for all propagating contractions [10.8 (1.5) mm vs 20.2 (5.9) mm, p = 0.01] and a lower post-meal increase in retrograde propagating contractions (p = 0.04). CONCLUSIONS: In this first high-resolution colonic manometry study of patients with diverticular disease, we did not find evidence for increased manometric pressures or increased colonic activity in patients with diverticular disease.

Changes in neuromuscular structure and functions of human colon during ageing are region-dependent.

OBJECTIVE: To determine if human colonic neuromuscular functions decline with increasing age. DESIGN: Looking for non-specific changes in neuromuscular function, a standard burst of electrical field stimulation (EFS) was used to evoke neuronally mediated (cholinergic/nitrergic) contractions/relaxations in ex vivomuscle strips of human ascending and descending colon, aged 35-91 years (macroscopically normal tissue; 239 patients undergoing cancer resection). Then, to understand mechanisms of change, numbers and phenotype of myenteric neurons (30 306 neurons stained with different markers), densities of intramuscular nerve fibres (51 patients in total) and pathways involved in functional changes were systematically investigated (by immunohistochemistry and use of pharmacological tools) in elderly (≥70 years) and adult (35-60 years) groups. RESULTS: With increasing age, EFS was more likely to evoke muscle relaxation in ascending colon instead of contraction (linear regression: n=109, slope 0.49%±0.21%/year, 95% CI), generally uninfluenced by comorbidity or use of medications. Similar changes were absent in descending colon. In the elderly, overall numbers of myenteric and neuronal nitric oxide synthase-immunoreactive neurons and intramuscular nerve densities were unchanged in ascending and descending colon, compared with adults. In elderly ascending, not descending, colon numbers of cell bodies exhibiting choline acetyltransferase immunoreactivity increased compared with adults (5.0±0.6 vs 2.4±0.3 neurons/mm myenteric plexus, p=0.04). Cholinergically mediated contractions were smaller in elderly ascending colon compared with adults (2.1±0.4 and 4.1±1.1 g-tension/g-tissue during EFS; n=25/14; p=0.04); there were no changes in nitrergic function or in ability of the muscle to contract/relax. Similar changes were absent in descending colon. CONCLUSION: In ascending not descending colon, ageing impairs cholinergic function.

Visceral hypersensitivity is associated with GI symptom severity in functional GI disorders: consistent findings from five different patient cohorts.

OBJECTIVE: Our aim was to evaluate the association between visceral hypersensitivity and GI symptom severity in large cohorts of patients with functional GI disorder (FGID) and to adjust for psychological factors and general tendency to report symptoms. DESIGN: We included five cohorts of patients with FGIDs (IBS or functional dyspepsia; n=1144), who had undergone visceral sensitivity testing using balloon distensions (gastric fundus, descending colon or rectum) and completed questionnaires to assess GI symptom severity, non-GI somatic symptoms, anxiety and depression. Subjects were divided into sensitivity tertiles based on pain/discomfort thresholds. GI symptom severity was compared between sensitivity tertiles in each cohort and corrected for somatisation, and anxiety and depression. RESULTS: In all five cohorts, GI symptom severity increased gradually with increasing visceral sensitivity, with significant differences in GI symptom severity between the sensitivity tertiles (p<0.0001), with small to medium effect sizes (partial η2: 0.047-0.11). The differences between sensitivity tertiles remained significant in all cohorts after correction for anxiety and depression, and also after correction for non-GI somatic symptom reporting in all of the cohorts (p<0.05). CONCLUSIONS: A gradual increase in GI symptom severity with increasing GI sensitivity was demonstrated in IBS and functional dyspepsia, which was consistent across several large patient groups from different countries, different methods to assess sensitivity and assessments in different parts of the GI tract. This association was independent of tendency to report symptoms or anxiety/depression comorbidity. These findings confirm that visceral hypersensitivity is a contributor to GI symptom generation in FGIDs.

Curcumin Inhibits 5-Fluorouracil-induced Up-regulation of CXCL1 and CXCL2 of the Colon Associated with Attenuation of Diarrhoea Development.

The compound 5-fluorouracil (5-FU) is used in cancer chemotherapy and is known to cause diarrhoea. We recently reported that chemokine (C-X-C motif) ligand 1 (CXCL1) and neutrophils in the colonic mucosa were markedly increased by the administration of 5-FU in mice. Curcumin has anti-inflammatory, antitumour and antioxidant properties. Therefore, we examined the effect of curcumin on 5-FU-induced diarrhoea development and CXCL1 and CXCL2 up-regulation in the colon. Mice were given 5-FU (50 mg/kg, i.p.) daily for 4 days. Curcumin (100 or 300 mg/kg, p.o.) was administered on the day before the first administration of 5-FU and administered 30 min. before the administration of 5-FU. Gene expression levels of CXCL1 and CXCL2 in the colon were examined by real-time RT-PCR. Curcumin reduced the 5-FU-induced diarrhoea development. Under this condition, the CXCL1 and CXCL2 gene up-regulated by 5-FU administration was inhibited by curcumin. The gene expression of CXCL1 and CXCL2 was also enhanced by 5-FU application in vitro. The 5-FU-induced up-regulated CXCL1 and CXCL2 gene expressions were inhibited by curcumin, Bay-117082 and bortezomib, nuclear factor kappa B (NF-κB) inhibitors, C646, a p300/cyclic adenosine monophosphate response element-binding protein-histone acetyltransferase (HAT) inhibitor. In conclusion, these findings suggested that curcumin prevented the development of diarrhoea by inhibiting NF-κB and HAT activation.

[Multivariate analysis of risk factors of the anal functional disorders after abdominal-anal resection with delayed formation of colonic-anal anastomosis].

Multivariate analysis of clinical factors was conducted on the material histories of 195 patients treated between 2004 and 2006. In Donetsk regional antitumor center, which for rectal cancer (RC) is made abdomino-anal resection of the rectum with the delayed formation koloanal anastomosis after bringing down the colon to the perineum. In 97 patients the operation was performed with the use of electric welding soft tissue (EWST), in 98--a standard way. Studied the quality of life of patients using a questionnaire QLQ C30-CR38 and the function of the anal incontinence (Wexner scale). It is established, that the greatest influence on the function of the anal continence have a view of a combined and complex treatment, radicality intervention, the method of forming koloanal of anastomosis. Application EWST the second stage of surgery to cut off excess relegated intestine helped reduce the risk of poor function of the anal continence.

[Colon transit time in children and young adults with open spinal dysraphism]. / Temps du transit colique chez l'enfant atteint de dysraphisme ouvert.

INTRODUCTION: Patients with open spinal dysraphism (OSD) frequently present constipation and incontinence requiring treatment. AIM: Evaluation of colon transit time (CTT) in patients with OSD, in relation to neural lesion, mobility, bowel habits, and continence status. METHODS: OSD patients aged between 6 and 20 years, who did not use antegrade enemas, were invited to participate in the study. Data from the medical file and information retrieved by questionnaires for constipation and incontinence were collected. The control group consisted of 13 healthy age-matched children. CTT was measured using the 6-day pellet method with an abdominal X-ray on day 7. Laxatives were continued and retrograde colon enemas were stopped 48h prior the X-ray. RESULTS: Thirty of the 33 patients who met the inclusion criteria agreed to participate. Twelve (40%) patients were constipated (Rome III criteria) despite treatment. Fifteen (50%) were continent, with or without treatment. Total CTT was significantly longer in OSD patients (median CTT: 86.4h vs. 43.2h controls). Constipated OSD patients had a significantly prolonged CTT compared to non-constipated patients (CTT: 125.4h vs. 51.6h). Spontaneous continent OSD patients had a normal CTT (CTT: 33.6h). An abnormal CTT predicted the necessity of treatment to achieve continence (P<0.006). CONCLUSION: CTT in OSD patients is significantly prolonged, indicating a neurogenic involvement of the bowel and a slow transit constipation. An abnormal CTT predicts the necessity of therapy to achieve fecal continence.

Intraoperative ischemia of the distal end of colon anastomoses as detected with visible light spectroscopy causes reduction of anastomotic strength.

BACKGROUND: To explore new methods for intraoperative evaluation of tissue oxygenation, we evaluated the use of visible light spectroscopy as a predictor of anastomotic strength in an experimental model with ischemic murine colon anastomoses. MATERIALS AND METHODS: Male rats (n = 34) were divided into 2 groups (ischemia and nonischemia). In the ischemia group the arteries of the distal colon were ligated until tissue oxygen saturation (StO2) dropped below 55%. A segment of the proximal part of the colon was resected until a well-perfused area was reached and an anastomosis was performed. In the nonischemia group, resection of a segment of descending colon and a colon anastomosis was performed. The animals were sacrificed on the 3rd or 7th postoperative d. The anastomosis was tested for bursting pressure and breaking strength. RESULTS: After ligation of the relevant mesenteric arteries, StO2 of the distal part of the colon decreased (54.6% SD 6.4% versus 71.2% SD 7.4%, P

Anorectal stimulation causes increased colonic motor activity in subjects with spinal cord injury.

BACKGROUND: Difficulty with evacuation (DWE) is a major problem after spinal cord injury (SCI). Stimulation of the anal canal and lower rectum, accomplished using a gloved finger (so-called digital rectal stimulation or DRS) is often used as an adjunct to laxatives and enemas to facilitate bowel evacuation. However, the basis for the efficacy of DRS is not known. This study assessed the effect of DRS on colonic motility. METHODS: Six subjects with SCI were studied several hours after a bowel care session. Colonic motility was assessed using a manometric catheter (affixed endoscopically to the splenic flexure) at baseline, during DRS, and after DRS. In addition, evacuation of barium oatmeal paste (with the consistency of stool and introduced into the rectum and descending colon) was assessed simultaneously using fluoroscopic techniques. RESULTS: The mean number (+/- SEM) of peristaltic waves per minute increased from 0 at baseline to 1.9 (+/- 0.5/min) during DRS and 1.5 (+/- 0.3/min) during the period immediately after cessation of DRS (P < 0.05). The mean amplitude (+/- SEM) of the peristaltic contractions was 43.4 (+/- 2.2) mmHg. The frequency of contractions, as well as amplitude of contractions, during or immediately after DRS was not significantly different. These manometric changes in response to DRS were accompanied by expulsion of barium oatmeal paste in every subject by the fifth DRS. CONCLUSIONS: DRS causes left-sided colonic activity in subjects with SCI. At least in part, an anorectal colonic reflex that results in enhanced contractions of the descending colon and rectum may contribute to bowel evacuation in individuals with SCI.