Peter A. Bampton

Crohn's disease management after intestinal resection: a randomised trial.

BACKGROUND Most patients with Crohns disease need an intestinal resection, but a majority will subsequently experience disease recurrence and require further surgery. This study aimed to identify the optimal strategy to prevent postoperative disease recurrence. METHODS In this randomised trial, consecutive patients from 17 centres in Australia and New Zealand undergoing intestinal resection of all macroscopic Crohns disease, with an endoscopically accessible anastomosis, received 3 months of metronidazole therapy. Patients at high risk of recurrence also received a thiopurine, or adalimumab if they were intolerant to thiopurines. Patients were randomly assigned to parallel groups: colonoscopy at 6 months (active care) or no colonoscopy (standard care). We used computer-generated block randomisation to allocate patients in each centre to active or standard care in a 2:1 ratio. For endoscopic recurrence (Rutgeerts score ≥i2) at 6 months, patients stepped-up to thiopurine, fortnightly adalimumab with thiopurine, or weekly adalimumab. The primary endpoint was endoscopic recurrence at 18 months. Patients and treating physicians were aware of the patients study group and treatment, but central reading of the endoscopic findings was undertaken blind to the study group and treatment. Analysis included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00989560. FINDINGS Between Oct 13, 2009, and Sept 28, 2011, 174 (83% high risk across both active and standard care groups) patients were enrolled and received at least one dose of study drug. Of 122 patients in the active care group, 47 (39%) stepped-up treatment. At 18 months, endoscopic recurrence occurred in 60 (49%) patients in the active care group and 35 (67%) patients in the standard care group (p=0.03). Complete mucosal normality was maintained in 27 (22%) of 122 patients in the active care group versus four (8%) in the standard care group (p=0.03). In the active care arm, of those with 6 months recurrence who stepped up treatment, 18 (38%) of 47 patients were in remission 12 months later; conversely, of those in remission at 6 months who did not change therapy recurrence occurred in 31 (41%) of 75 patients 12 months later. Smoking (odds ratio [OR] 2.4, 95% CI 1.2-4.8, p=0.02) and the presence of two or more clinical risk factors including smoking (OR 2.8, 95% CI 1.01-7.7, p=0.05) increased the risk of endoscopic recurrence. The incidence and type of adverse and severe adverse events did not differ significantly between patients in the active care and standard care groups (100 [82%] of 122 vs 45 [87%] of 52; p=0.51) and (33 [27%] of 122 vs 18 [35%] of 52; p=0.36), respectively. INTERPRETATION Treatment according to clinical risk of recurrence, with early colonoscopy and treatment step-up for recurrence, is better than conventional drug therapy alone for prevention of postoperative Crohns disease recurrence. Selective immune suppression, adjusted for early recurrence, rather than routine use, leads to disease control in most patients. Clinical risk factors predict recurrence, but patients at low risk also need monitoring. Early remission does not preclude the need for ongoing monitoring. FUNDING AbbVie, Gutsy Group, Gandel Philanthropy, Angior Foundation, Crohns Colitis Australia, and the National Health and Medical Research Council.

Comparison of a brush‐sampling fecal immunochemical test for hemoglobin with a sensitive guaiac‐based fecal occult blood test in detection of colorectal neoplasia

Fecal immunochemical tests (FIT) are an advanced fecal occult blood test (FOBT) technology that reduces barriers to population screening by simplifying the logistics of stool‐sampling. The current study was conducted to undertake a paired comparison of a sensitive guaiac FOBT (GFOBT; Hemoccult II Sensa, Beckman Coulter, Fullerton, CA) with a brush‐sampling FIT (InSure; Enterix, North Ryde, NSW, Australia), to determine whether this FIT improves detection of significant neoplasia.

Spatial and temporal organization of pressure patterns throughout the unprepared colon during spontaneous defecation

OBJECTIVE:The aim of this study was to examine colonic motor events associated with spontaneous defecation in the entire unprepared human colon under physiological conditions.METHODS: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.RESULTS: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).CONCLUSIONS: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.

Prolonged multi-point recording of colonic manometry in the unprepared human colon: providing insight into potentially relevant pressure wave parameters

OBJECTIVES: To determine the feasibility of and derive normative data for prolonged, 24-h, multipoint, closely spaced, water perfused manometry of the unprepared human colon. METHODS: In 14 healthy volunteers, 24-h recordings were made using a water perfused, balloon-tipped, 17 lumen catheter which was passed pernasally and positioned so that 16 recording sites spanned the colon at 7.5 cm intervals from cecum to rectum. The area under the pressure curve and propagating pressure wave parameters were quantified for the 16 regions. High amplitude propagating sequences were defined as were rectal motor complexes. RESULTS: Nasocolonic recording was well tolerated and achievable. Propagation sequences, including high amplitude propagating sequences, originated in the cecum (0.32 ± 0.05/h) more frequently than in other regions and the extent of propagation correlated significantly with proximity of the site of sequence origin to the cecum (p < 0.001). Propagation velocity of propagating sequences was greater than high amplitude propagating sequences (p = 0.0002) and region-dependent, unlike high amplitude propagating sequences (p < 0.01). The frequency of propagating sequences did not increase after the meal, but frequency of high amplitude propagating sequences was increased significantly by the meal (p < 0.01). Rectal motor complexes were seen throughout the colon with no apparent periodicity. CONCLUSIONS: Prolonged, multipoint, perfusion manometry of the unprepared colon provides improved spatial resolution of colonic motor patterns and confirms the diurnal and regional variations in propagating pressure waves detected in the prepared colon. The study demonstrates differences between high amplitude propagating sequences and propagating sequence parameters that may have functional significance; and also, that the rectal motor complex is a ubiquitous pan colonic motor pattern.

Effect of Relaxation Music on Patient Tolerance of Gastrointestinal Endoscopic Procedures

The use of relaxation music as an adjunct to sedation has not been well studied. We tried to determine whether the use of relaxation music can improve patient tolerance of gastrointestinal endoscopic procedures. Fifty-nine patients undergoing gastrointestinal endoscopic procedures were randomly assigned to receive either relaxation music (n = 28) or no music (n = 31) using headphones and a portable compact disc player. Patient anxiety before the procedure, tolerance of the procedure, and willingness to undergo a repeated procedure were self-assessed using a visual analog scale. Patient tolerance was also assessed by the assisting nurse. There was no significant difference in the overall tolerance score between the two groups. However, a significantly higher proportion of patients described the experience of a gastrointestinal endoscopic procedure as being at least moderately unpleasant in the no-music group. Patient acceptance of the relaxation music was high: 82% in the group stated they would have music again if they required another procedure. We conclude that, even in patients who have sedation, relaxation music can reduce the number who find the experience of gastrointestinal endoscopic procedures unpleasant. Therefore we believe it has a role as an adjunct to sedation in gastrointestinal endoscopic procedures.

HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants

Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07–3.26, P = 2 × 10−16). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the HLA region identified association with the HLA-DQA1*02:01–HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk.

Interval faecal occult blood testing in a colonoscopy based screening programme detects additional pathology

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.

Serious infections in patients with inflammatory bowel disease receiving anti‐tumor‐necrosis‐factor‐alpha therapy: An Australian and New Zealand experience

Background and Aim:  Anti‐tumor‐necrosis‐factor‐alpha (anti‐TNF‐α) medications are effective in inflammatory bowel disease (IBD), but have an increased risk of tuberculosis (TB) and serious infections. The aim of this study was to examine the Australian/New Zealand experience of serious infections and TB in IBD patients receiving anti‐TNF‐α therapy from 1999–2009.

Quantification of in vivo colonic motor patterns in healthy humans before and after a meal revealed by high-resolution fiber-optic manometry.

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.

Interval Fecal Immunochemical Testing in a Colonoscopic Surveillance Program Speeds Detection of Colorectal Neoplasia

BACKGROUND & AIMS Rapidly progressing or missed lesions can reduce the effectiveness of colonoscopy-based colorectal cancer surveillance programs. We investigated whether giving fecal immunochemical tests (FITs) for hemoglobin between surveillance colonoscopies resulted in earlier detection of neoplasia. METHODS The study included 1736 patients with a family history or past neoplasia; they received at least 2 colonoscopy examinations and were followed for a total of 8863 years. Patients were excluded from the study if they had genetic syndromes, colorectal surgery, or inflammatory bowel disease. An FIT was offered yearly, in the interval between colonoscopies; if results were positive, the colonoscopy was performed earlier than scheduled. RESULTS Among the 1071 asymptomatic subjects (61%) who received at least 1 FIT, the test detected 12 of 14 cancers (86% sensitivity) and 60 of 96 (63%) advanced adenomas. In patients with positive results from the FIT, the diagnosis of cancer was made 25 months (median) earlier and diagnosis of advanced adenoma 24 months earlier. Patients who had repeated negative results from FIT had an almost 2-fold decrease in risk for cancer and advanced adenoma compared with patients who were not tested (5.5% vs 10.1%, respectively, P = .0004). The most advanced stages of neoplasia, observed across the continuum from nonadvanced adenoma to late-stage cancer, were associated with age (increased with age), sex (increased in males), and FIT result. The probability of most advanced neoplastic stage was lowest among those with a negative result from the FIT (odds ratio, 0.68; P < .001). CONCLUSIONS Interval examinations using the FIT detected neoplasias sooner than scheduled surveillances. Subjects with negative results from the FIT had the lowest risk for the most advanced stage of neoplasia. Interval FIT analyses can be used to detect missed or rapidly developing lesions in surveillance programs.