Background
Until recently, investigations of the normal patterns of motility of the healthy human colon have been limited by the resolution of in vivo recording techniques.
Methods
We have used a ...new, high‐resolution fiber‐optic manometry system (72 sensors at 1‐cm intervals) to record motor activity from colon in 10 healthy human subjects.
Key Results
In the fasted colon, on the basis of rate and extent of propagation, four types of propagating motor pattern could be identified: (i) cyclic motor patterns (at 2–6/min); (ii) short single motor patterns; (iii) long single motor patterns; and (iv) occasional retrograde, slow motor patterns. For the most part, the cyclic and short single motor patterns propagated in a retrograde direction. Following a 700 kCal meal, a fifth motor pattern appeared; high‐amplitude propagating sequences (HAPS) and there was large increase in retrograde cyclic motor patterns (5.6 ± 5.4/2 h vs 34.7 + 19.8/2 h; p < 0.001). The duration and amplitude of individual pressure events were significantly correlated. Discriminant and multivariate analysis of duration, gradient, and amplitude of the pressure events that made up propagating motor patterns distinguished clearly two types of pressure events: those belonging to HAPS and those belonging to all other propagating motor patterns.
Conclusions & Inferences
This work provides the first comprehensive description of colonic motor patterns recorded by high‐resolution manometry and demonstrates an abundance of retrograde propagating motor patterns. The propagating motor patterns appear to be generated by two independent sources, potentially indicating their neurogenic or myogenic origin.
This work provides the first comprehensive description of colonic motor patterns recorded by high‐resolution manometry and demonstrates an abundance of retrograde propagating motor patterns. The propagating motor patterns appear to be generated by two independent sources, potentially indicating their neurogenic or myogenic origin.
Summary
Background Ileus occurs after abdominal surgery and may be severe. Inhibition of prostaglandin release reduces post‐operative ileus in a rat model.
Aim To determine whether prostaglandin ...inhibition by cyclooxygenase inhibitors, celecoxib or diclofenac, could enhance gastrointestinal recovery and reduce post‐operative ileus in humans.
Methods Two hundred and ten patients undergoing elective major abdominal surgery were randomized to receive twice daily placebo (n = 67), celecoxib (100 mg, n = 74) or diclofenac (50 mg, n = 69), preoperatively and continuing for up to 7 days. Primary outcomes were hallmarks of gut recovery. Secondary outcomes were paralytic ileus, pain and complications.
Results There was no clinically significant difference between the groups for restoration of bowel function. There was a significant reduction in paralytic ileus in the celecoxib‐treated group (n = 1, 1%) compared with diclofenac (n = 7, 10%) and placebo (n = 9, 13%); P = 0.025, RR 0.20, CI 0.01–0.77. Pain scores, analgesia, transfusion requirements and adverse event rates were similar between study groups.
Conclusions Perioperative low dose celecoxib, but not diclofenac, markedly reduced the development of paralytic ileus following major abdominal surgery, but did not accelerate early recovery of bowel function. This was independent of narcotic use and had no increase in post‐operative complications.
Summary
Background
Crohn's disease recurs in the majority of patients after intestinal resection.
Aim
To compare the relative efficacy of thiopurines and anti‐TNF therapy in patients at high risk of ...disease recurrence.
Methods
As part of a larger study comparing post‐operative management strategies, patients at high risk of recurrence (smoker, perforating disease, ≥2nd operation) were treated after resection of all macroscopic disease with 3 months metronidazole together with either azathioprine 2 mg/kg/day or mercaptopurine 1.5 mg/kg/day. Thiopurine‐intolerant patients received adalimumab induction then 40 mg fortnightly. Patients underwent colonoscopy at 6 months with endoscopic recurrence assessed blind to treatment.
Results
A total of 101 patients 50% male; median (IQR) age 36 (25–46) years were included. There were no differences in disease history between thiopurine‐ and adalimumab‐treated patients. Fifteen patients withdrew prior to 6 months, five due to symptom recurrence (of whom four were colonoscoped). Endoscopic recurrence (Rutgeerts score i2–i4) occurred in 33 of 73 (45%) thiopurine vs. 6 of 28 (21%) adalimumab‐treated patients intention‐to‐treat (ITT); P = 0.028 or 24 of 62 (39%) vs. 3 of 24 (13%) respectively per‐protocol analysis (PPA); P = 0.020. Complete mucosal endoscopic normality (Rutgeerts i0) occurred in 17/73 (23%) vs. 15/28 (54%) (ITT; P = 0.003) and in 27% vs. 63% (PPA; P = 0.002). The most advanced disease (Rutgeerts i3 and i4) occurred in 8% vs. 4% (thiopurine vs. adalimumab).
Conclusions
In Crohn's disease patients at high risk of post‐operative recurrence adalimumab is superior to thiopurines in preventing early disease recurrence.
Background
Slow transit constipation (STC) is associated with colonic motor abnormalities. The underlying cause(s) of the abnormalities remain poorly defined. In health, utilizing high resolution ...fiber‐optic manometry, we have described a distal colonic propagating motor pattern with a slow wave frequency of 2–6 cycles per minute (cpm). A high calorie meal caused a rapid and significant increase in this activity, suggesting the intrinsic slow wave activity could be mediated by extrinsic neural input. Utilizing the same protocol our aim was to characterize colonic meal response STC patients.
Methods
A fiber‐optic manometry catheter (72 sensors at 1 cm intervals) was colonoscopically placed with the tip clipped at the ascending or transverse colon, in 14 patients with scintigraphically confirmed STC. Manometric recordings were taken, for 2 h pre and post a 700 kCal meal. Data were compared to 12 healthy adults.
Key Results
Prior to and/or after the meal the cyclic propagating motor pattern was identified in 13 of 14 patients. However, the meal, did not increase the cyclic motor pattern (preprandial 7.4 ± 7.6 vs postprandial 8.3 ± 4.5 per/2 h), this is in contrast to the dramatic increase observed in health (8.3 ± 13.3 vs 59.1 ± 89.0 per/2 h; p < 0.001).
Conclusions & Inferences
In patients with STC a meal fails to induce the normal increase in the distal colonic cyclic propagating motor patterns. We propose that these data may indicate that the normal extrinsic parasympathetic inputs to the colon are attenuated in these patients.
Utilizing fiber‐optic, high resolution colonic manometry, in patients with slow transit constipation, we have defined the colonic motor abnormalities in response to a high calorie meal. We propose a hypothesis that a possible neuropathy in the extrinsic parasympathetic inputs to the colon of patients with slow transit constipation may exist.
We aimed to determine whether rectal distension and/or infusion of bile acids stimulates propagating or nonpropagating activity in the unprepared proximal colon in 10 healthy volunteers using a ...nasocolonic manometric catheter (16 recording sites at 7.5-cm spacing). Sensory thresholds and proximal colonic motor responses were assessed following rectal distension by balloon inflation and rectal instillation of chenodeoxycholic acid. Maximum tolerated balloon volume and the volume that stimulated a desire to defecate were both significantly (P < 0.01) reduced after rectal chenodeoxycholic acid. The frequency of colonic propagating pressure wave sequences decreased significantly in response to initial balloon inflations (P < 0.05), but the frequency doubled after subsequent chenodeoxycholic acid infusion (P < 0.002). Nonpropagating activity decreased after balloon inflation, was not influenced by acid infusion, and demonstrated a further decrease in response to repeat balloon inflation. We concluded that rectal chenodeoxycholic acid in physiological concentrations is a potent stimulus for propagating pressure waves arising in the proximal colon and reduces rectal sensory thresholds. Rectal distension inhibits all colonic motor activity.
Background: Colonoscopic based surveillance is recommended for patients at increased risk of colorectal cancer. The appropriate interval between surveillance colonoscopies remains in debate, as is ...the “miss rate” for colorectal cancer within such screening programmes. Aims: The main aim of this study was to determine whether a one-off interval faecal occult blood test (FOBT) facilitates the detection of significant neoplasia within a colonoscopic based surveillance programme. Secondary aims were to determine if invitees were interested in participating in interval screening, and to determine whether interval lesions were missed or whether they developed rapidly since the previous colonoscopy Patients: Patients enrolled in a colonoscopic based screening programme due to a personal history of colorectal neoplasia or a significant family history. Methods: Patients within the screening programme were invited to perform an immunochemical FOBT (Inform). A positive result was followed by colonoscopy; significant neoplasia was defined as colorectal cancer, adenomas either ⩾10 mm or with a villous component, high grade dysplasia, or multiplicity (⩾3 adenomas). Participation rates were determined for age, sex, and socioeconomic subgroups. Colonoscopy recall databases were examined to determine the interval between previous colonoscopy and FOBT offer, and correlations between lesion characteristics and interval time were determined. Results: A total of 785 of 1641 patients invited (47.8%) completed an Inform kit. A positive result was recorded for 57 (7.3%). Fifty two of the 57 test positive patients completed colonoscopy; 14 (1.8% of those completing the FOBT) had a significant neoplastic lesion. These consisted of six colorectal cancers and eight significant adenomas. Conclusions: A one off immunochemical faecal occult blood test within a colonoscopy based surveillance programme had a participation rate of nearly 50% and appeared to detect additional pathology, especially in patients with a past history of colonic neoplasia.
To examine the compliance of colorectal cancer surveillance decisions for individuals at greater risk with current evidence-based guidelines and to determine whether compliance differs between ...surveillance models.
Prospective auditing of compliance of surveillance decisions with evidence-based guidelines (NHMRC) in two decision-making models: nurse coordinator-led decision making in public academic hospitals and physician-led decision making in private non-academic hospitals.
Selected South Australian hospitals participating in the Southern Co-operative Program for the Prevention of Colorectal Cancer (SCOOP).
Proportions of recall recommendations that matched NHMRC guideline recommendations (March-May 2015); numbers of surveillance colonoscopies undertaken more than 6 months ahead of schedule (January-December 2015); proportions of significant neoplasia findings during the 15 years of SCOOP operation (2000-2015).
For the nurse-led/public academic hospital model, the recall interval recommendation following 398 of 410 colonoscopies (97%) with findings covered by NHMRC guidelines corresponded to the guideline recommendations; for the physician-led/private non-academic hospital model, this applied to 257 of 310 colonoscopies (83%) (P < 0.001). During 2015, 27% of colonoscopies in public academic hospitals (mean, 27 months; SD, 13 months) and 20% of those in private non-academic hospitals (mean, 23 months; SD, 12 months) were performed more than 6 months earlier than scheduled, in most cases because of patient-related factors (symptoms, faecal occult blood test results). The ratio of the numbers of high risk adenomas to cancers increased from 6.6:1 during 2001-2005 to 16:1 during 2011-2015.
The nurse-led/public academic hospital model for decisions about colorectal cancer surveillance intervals achieves a high degree of compliance with guideline recommendations, which should relieve burdening of colonoscopy resources.
Background
Endoscopic surveillance of Barrett’s esophagus (BE) is probably not cost-effective. A sub-population with BE at increased risk of high-grade dysplasia (HGD) or esophageal adenocarcinoma ...(EAC) who could be targeted for cost-effective surveillance was sought.
Methods
The outcome for BE surveillance from 2003 to 2012 in a structured program was reviewed. Incidence rates and incidence rate ratios for developing HGD or EAC were calculated. Risk stratification identified individuals who could be considered for exclusion from surveillance. A health-state transition Markov cohort model evaluated the cost-effectiveness of focusing on higher-risk individuals.
Results
During 2067 person-years of follow-up of 640 patients, 17 individuals progressed to HGD or EAC (annual IR 0.8%). Individuals with columnar-lined esophagus (CLE) ≥2 cm had an annual IR of 1.2% and >8-fold increased relative risk of HGD or EAC, compared to CLE <2 cm IR—0.14% (IRR 8.6, 95% CIs 4.5–12.8). Limiting the surveillance cohort after the first endoscopy to individuals with CLE ≥2 cm, or dysplasia, followed by a further restriction after the second endoscopy—exclusion of patients without intestinal metaplasia—removed 296 (46%) patients, and 767 (37%) person-years from surveillance. Limiting surveillance to the remaining individuals reduced the incremental cost-effectiveness ratio from US$60,858 to US$33,807 per quality-adjusted life year (QALY). Further restrictions were tested but failed to improve cost-effectiveness.
Conclusions
Based on stratification of risk, the number of patients requiring surveillance can be reduced by at least a third. At a willingness-to-pay threshold of US$50,000 per QALY, surveillance of higher-risk individuals becomes cost-effective.
Despite its size and physiological importance, the human colon is one of the least understood organs of the body. Many disorders arise from suspected abnormalities in colonic contractions, yet, due ...largely to technical constraints, investigation of human colonic motor function still remains relatively primitive. Most measures of colonic motility focus upon the transit speed (radiology, scintigraphy and, more recently, “smart pills”); however, only colonic manometry can measure pressure/force from multiple regions within the colon in real time (Dinning and Scott (Curr Opin Pharmacol 11:624–629,
2011
)). Based upon data from colonic manometry studies, a number of different colonic motor patterns have been distinguished: (1) antegrade high amplitude propagating sequences (contractions), (2) low amplitude propagating sequences, (3) non-propagating contractions, and (4) and rarely episodes of retrograde (oral) propagating pressure waves (Dining and Di Lorenzo (Best Pract Res Clin Gastrolenterol 25(1): 89–101,
2011
)). Abnormalities in the characteristics of these motor patterns should help to characterize dysmotility in a patient populations, and in both adults and children colonic motor abnormalities have been identified with manometry studies (Rao et al. Am J Gastroenterol 99(12):2405–2416, (
2004
), Di Lorenzo et al. Gut. 34(1): 803–807, (
1993
)). Yet, despite more than two decades of such studies, the clinical utility of colonic manometry remains marginal with no specific manometric biomarkers of colonic dysfunction being established (Camilleri et al. Neurogastroenterol Motil. 20(12): 1269–1282,
2008
). This has been highlighted recently in a colonic manometry study by Singh et al. (
2013
), in which 41 % of 80 patients, with confirmed slow transit constipation, were reported to have normal motility. While this may suggest that no motor abnormalities exist in a proportion of such patients, the finding may also reflect technical constraints in our ability to detail colonic motility patterns.
The aim of this study was to examine colonic motor events associated with spontaneous defecation in the entire unprepared human colon under physiological conditions.
In 13 healthy volunteers a ...perfused, balloon-tipped, 17-lumen catheter (outer diameter, 3.5 mm; intersidehole spacing, 7.5 cm) was passed pernasally and positioned in the distal unprepared colon.
In the hour before spontaneous defecation, there was an increase in propagating sequence frequency (p = 0.04) and nonpropagating activity when compared to basal conditions (p < 0.0001). During this hour the spatial and temporal relationships among propagating sequences demonstrated a biphasic pattern. Both the early (proximal) and late (distal) colonic phases involved the whole colon and were characterized by respective antegrade and retrograde migration of site-of-origin of arrays of propagating sequences. There was a negative correlation between propagating sequence amplitude and the time interval from propagating sequence to stool expulsion (p = 0.008).
The colonic motor correlate of defecation is the colonic propagating sequence, the frequency and amplitude of which begin to increase as early as 1 h before stool expulsion. During the preexpulsive phase, the spatial and temporal relationship among the sites of origin of individual propagating sequences demonstrate a stereotypic anal followed by orad migration, which raises the possibility of control by long colocolonic pathways.
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