Julian Teare

A Meta-analysis on the Influence of Inflammatory Bowel Disease on Pregnancy

Background: Inflammatory bowel disease (IBD) has a typical onset during the peak reproductive years. Evidence of the risk of adverse pregnancy outcomes in IBD is important for the management of pregnancy to assist in its management. Aim: To provide a clear assessment of risk of adverse outcomes during pregnancy in women with IBD. Design: The Medline literature was searched to identify studies reporting outcomes of pregnancy in patients with IBD. Random-effect meta-analysis was used to compare outcomes between women with IBD and normal controls. Patients and setting: A total of 3907 patients with IBD (Crohn’s disease 1952 (63%), ulcerative colitis 1113 (36%)) and 320 531 controls were reported in 12 studies that satisfied the inclusion criteria. Results: For women with IBD, there was a 1.87-fold increase in incidence of prematurity (<37 weeks gestation; 95% CI 1.52 to 2.31; p<0.001) compared with controls. The incidence of low birth weight (<2500 g) was over twice that of normal controls (95% CI 1.38 to 3.19; p<0.001). Women with IBD were 1.5 times more likely to undergo caesarean section (95% CI 1.26 to 1.79; p<0.001), and the risk of congenital abnormalities was found to be 2.37-fold increased (95% CI 1.47 to 3.82; p<0.001). Conclusion: The study has shown a higher incidence of adverse pregnancy outcomes in patients with IBD. Further studies are required to clarify which women are at higher risk, as this was not determined in the present study. This has an effect on the management of patients with IBD during pregnancy, who should be treated as a potentially high-risk group.

Diagnostic Precision of Fecal Calprotectin for Inflammatory Bowel Disease and Colorectal Malignancy

OBJECTIVES:Fecal calprotectin (FC) is a relatively new marker of intraluminal intestinal inflammation. Using meta-analytical techniques, the study aimed to evaluate the diagnostic precision of FC for inflammatory bowel disease (IBD) and colorectal cancer (CRC) in adults and children.METHODS:Quantitative meta-analysis was performed on prospective studies, comparing FC levels against the histological diagnosis. Sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated for each study. Summary receiver-operating characteristic (sROC) curves and subgroup analysis were undertaken. Study quality and heterogeneity were evaluated.RESULTS:Thirty studies of 5,983 patients were included. FC levels in patients with IBD were higher by 219.2 micrograms per gram (μg/g) compared with normal patients (P < 0.001). sROC curve analysis showed a sensitivity of 0.95 (95% CI 0.93–0.97), specificity of 0.91 (95% CI 0.86–0.91), and an area under the curve (AUC) of 0.95 for the diagnosis of IBD. Patients with colorectal neoplasia had nonsignificantly higher FC levels by 132.2 μg/g compared with noncancer controls (P = 0.18). Sensitivity and specificity of FC for the diagnosis of CRC were 0.36 and 0.71, respectively, with an AUC of 0.66. The diagnostic precision of FC for IBD was higher in children than adults with better accuracy at a cutoff level of 100 μg/g versus 50 μg/g. Sensitivity analysis and metaregression analysis did not significantly alter the results.CONCLUSIONS:FC cannot be recommended as a screening test for CRC in the general population. FC appeared to offer a good diagnostic precision in distinguishing IBD from non-IBD diagnoses, with higher precision at a cutoff of 100 μg/g.

The Risk of Cancer in Patients with Crohn’s Disease

PurposeThe risk of cancer in patients with Crohn’s disease is not well defined. Using meta-analytical techniques, the present study was designed to quantify the risk of intestinal, extraintestinal, and hemopoietic malignancies in such patients.MethodsA literature search identified 34 studies of 60,122 patients with Crohn’s disease. The incidence and relative risk of cancer were calculated for patients with Crohn’s disease and compared with the baseline population of patients without Crohn’s disease. Overall pooled estimates, with 95 percent confidence intervals, were obtained, using a random-effects model.ResultsThe relative risk of small bowel, colorectal, extraintestinal cancer, and lymphoma compared with the baseline population was 28.4 (95 percent confidence interval, 14.46–55.66), 2.4 (95 percent confidence interval, 1.56–4.36), 1.27 (95 percent confidence interval, 1.1–1.47), and 1.42 (95 percent confidence interval, 1.16–1.73), respectively. On subgroup analysis, patients with Crohn’s disease had an increased risk of colon cancer (relative risk, 2.59; 95 percent confidence interval, 1.54–4.36) but not of rectal cancer (relative risk, 1.46; 95 percent confidence interval, 0.8–2.55). There was significant association between the anatomic location of the diseased bowel and the risk of cancer in that segment. The risk of small bowel cancer and colorectal cancer was found to be higher in North America and the United Kingdom than in Scandinavian countries with no evidence of temporal changes in the cancer incidence.ConclusionsThe present meta-analysis demonstrated an increased risk of small bowel, colon, extraintestinal cancers, and lymphoma in patients with Crohn’s disease. Patients with extensive colonic disease that has been present from a young age should be candidates for endoscopic surveillance; however, further data are required to evaluate the risk of neoplasia over time.

The Risk of Oral Contraceptives in the Etiology of Inflammatory Bowel Disease: A Meta-Analysis

OBJECTIVES:Several environmental and genetic factors have been implicated to date in the development of Crohns disease (CD) and ulcerative colitis (UC). The aim of this study was to provide a quantification of the risk of oral contraceptive pill (OCP) use in the etiology of inflammatory bowel disease.METHODS:A literature search was performed to identify comparative studies reporting on the association of oral contraceptive use in the etiology of UC and CD between 1983 and 2007. A random-effect meta-analysis was used to compare the incidence of UC or CD between the patients exposed to the OCP and nonexposed patients. The results were adjusted for smoking.RESULTS:A total of 75,815 patients were reported on by 14 studies, with 36,797 exposed to OCP and 39,018 nonexposed women. The pooled relative risk (RR) for CD for women currently taking the OCP was 1.51 (95% confidence interval [CI] 1.17–1.96, P = 0.002), and 1.46 (95% CI 1.26–1.70, P < 0.001), adjusted for smoking. The RR for UC in women currently taking the OCP was 1.53 (95% CI 1.21–1.94, P = 0.001), and 1.28 (95% CI 1.06–1.54, P = 0.011), adjusted for smoking. The RR for CD increased with the length of exposure to OCP. Moreover, although the RR did not reduce once the OCP was stopped, it was no longer significant once the OCP was stopped (CI contains 1), both for CD and for UC.CONCLUSIONS:This study provides evidence of an association between the use of oral contraceptive agents and development of IBD, in particular CD. The study also suggests that the risk for patients who stop using the OCP reverts to that of the nonexposed population.

The effect of restorative proctocolectomy on sexual function, urinary function, fertility, pregnancy and delivery: a systematic review.

PurposeThis study was designed to evaluate the effect of restorative proctocolectomy on sexual function, urinary function, fertility, pregnancy, and delivery in patients with ulcerative colitis.MethodsA systematic literature search was performed of articles published between 1980 and 2005 on patients undergoing restorative proctocolectomy for ulcerative colitis reporting data on the outcomes of interest. A random-effect, meta-analytical model was used for pooled estimates and 95 percent confidence intervals.ResultsA total of 22 studies, with 1,852 females, were included. Infertility rate was 12 percent before restorative proctocolectomy and 26 percent after, among 945 patients in seven studies. The incidence of sexual dysfunction was 8 percent preoperatively and 25 percent postoperatively (7 studies, n = 419). Two studies (n = 62) reported no urinary dysfunction in patients undergoing restorative proctocolectomy. There was an increased incidence of cesarean section after restorative proctocolectomy. During the third trimester of pregnancy, there was an increase in stool frequency by 1.15 stools per day compared with before pregnancy frequency (n = 49 95 percent confidence interval, 0.28–2.03 P = 0.01 chi-squared statistic, 0.04 P = 0.84). No significant differences were seen in pouch function after vaginal delivery (n = 456; weighted mean difference, 0.23; 95 percent confidence interval, 0.43–0.88; P = 0.49; chi-squared statistic, 1.29; P = 0.26).ConclusionsThe incidence of dyspareunia increases after restorative proctocolectomy. There was a decrease in fertility after restorative proctocolectomy. Pregnancy after restorative proctocolectomy was not associated with an increase in complications. There was an increase in stool frequency and pad usage during the third trimester. Vaginal delivery is safe after restorative proctocolectomy. Pouch function after delivery returns to pregestational function within six months.

Computed tomographic colonography versus colonoscopy for investigation of patients with symptoms suggestive of colorectal cancer (SIGGAR): a multicentre randomised trial

BACKGROUND Colonoscopy is the gold-standard test for investigation of symptoms suggestive of colorectal cancer; computed tomographic colonography (CTC) is an alternative, less invasive test. However, additional investigation after CTC is needed to confirm suspected colonic lesions, and this is an important factor in establishing the feasibility of CTC as an alternative to colonoscopy. We aimed to compare rates of additional colonic investigation after CTC or colonoscopy for detection of colorectal cancer or large (≥10 mm) polyps in symptomatic patients in clinical practice. METHODS This pragmatic multicentre randomised trial recruited patients with symptoms suggestive of colorectal cancer from 21 UK hospitals. Eligible patients were aged 55 years or older and regarded by their referring clinician as suitable for colonoscopy. Patients were randomly assigned (2:1) to colonoscopy or CTC by computer-generated random numbers, in blocks of six, stratified by trial centre and sex. We analysed the primary outcome-the rate of additional colonic investigation-by intention to treat. The trial is an International Standard Randomised Controlled Trial, number 95152621. FINDINGS 1610 patients were randomly assigned to receive either colonoscopy (n=1072) or CTC (n=538). 30 patients withdrew consent, leaving for analysis 1047 assigned to colonoscopy and 533 assigned to CTC. 160 (30.0%) patients in the CTC group had additional colonic investigation compared with 86 (8.2%) in the colonoscopy group (relative risk 3.65, 95% CI 2.87-4.65; p<0.0001). Almost half the referrals after CTC were for small (<10 mm) polyps or clinical uncertainty, with low predictive value for large polyps or cancer. Detection rates of colorectal cancer or large polyps in the trial cohort were 11% for both procedures. CTC missed 1 of 29 colorectal cancers and colonoscopy missed none (of 55). Serious adverse events were rare. INTERPRETATION Guidelines are needed to reduce the referral rate after CTC. For most patients, however, CTC provides a similarly sensitive, less invasive alternative to colonoscopy. FUNDING NIHR Health Technology Assessment Programme, NIHR Biomedical Research Centres funding scheme, Cancer Research UK, EPSRC Multidisciplinary Assessment of Technology Centre for Healthcare, and NIHR Collaborations for Leadership in Applied Health Research and Care.

Characterization of Inflammatory Bowel Disease With Urinary Metabolic Profiling

OBJECTIVES:Distinguishing between the inflammatory bowel disease (IBD), Crohns disease (CD), and ulcerative colitis (UC) is important for both management and prognostic reasons. Discrimination using noninvasive techniques could be an adjunct to conventional diagnostics. Differences have been shown between the intestinal microbiota of CD and UC patients and controls; the gut bacteria influence specific urinary metabolites that are quantifiable using proton high-resolution nuclear magnetic resonance (NMR) spectroscopy. This study tested the hypothesis that such metabolites differ between IBD and control cohorts, and that using multivariate pattern-recognition analysis, the cohorts could be distinguished by urine NMR spectroscopy.METHODS:NMR spectra were acquired from urine samples of 206 Caucasian subjects (86 CD patients, 60 UC patients, and 60 healthy controls). Longitudinal samples were collected from 75 individuals. NMR resonances specific for metabolites influenced by the gut microbes were studied, including hippurate, formate, and 4-cresol sulfate. Multivariate analysis of all urinary metabolites involved principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA).RESULTS:Hippurate levels were lowest in CD patients and differed significantly between the three cohorts (P<0.0001). Formate levels were higher and 4-cresol sulfate levels lower in CD patients than in UC patients or controls (P=0.0005 and P=0.0002, respectively). PCA revealed clustering of the groups; PLS-DA modeling was able to distinguish the cohorts. These results were independent of medication and diet and were reproducible in the longitudinal cohort.CONCLUSIONS:Specific urinary metabolites related to gut microbial metabolism differ between CD patients, UC patients, and controls. The emerging technique of urinary metabolic profiling with multivariate analysis was able to distinguish these cohorts.

Computed tomographic colonography versus barium enema for diagnosis of colorectal cancer or large polyps in symptomatic patients (SIGGAR): a multicentre randomised trial

BACKGROUND Barium enema (BE) is widely available for diagnosis of colorectal cancer despite concerns about its accuracy and acceptability. Computed tomographic colonography (CTC) might be a more sensitive and acceptable alternative. We aimed to compare CTC and BE for diagnosis of colorectal cancer or large polyps in symptomatic patients in clinical practice. METHODS This pragmatic multicentre randomised trial recruited patients with symptoms suggestive of colorectal cancer from 21 UK hospitals. Eligible patients were aged 55 years or older and regarded by their referring clinician as suitable for radiological investigation of the colon. Patients were randomly assigned (2:1) to BE or CTC by computer-generated random numbers, in blocks of six, stratified by trial centre and sex. We analysed the primary outcome-diagnosis of colorectal cancer or large (≥10 mm) polyps-by intention to treat. The trial is an International Standard Randomised Controlled Trial, number 95152621. FINDINGS 3838 patients were randomly assigned to receive either BE (n=2553) or CTC (n=1285). 34 patients withdrew consent, leaving for analysis 2527 assigned to BE and 1277 assigned to CTC. The detection rate of colorectal cancer or large polyps was significantly higher in patients assigned to CTC than in those assigned to BE (93 [7.3%] of 1277 vs 141 [5.6%] of 2527, relative risk 1.31, 95% CI 1.01-1.68; p=0.0390). CTC missed three of 45 colorectal cancers and BE missed 12 of 85. The rate of additional colonic investigation was higher after CTC than after BE (283 [23.5%] of 1206 CTC patients had additional investigation vs 422 [18.3%] of 2300 BE patients; p=0.0003), due mainly to a higher polyp detection rate. Serious adverse events were rare. INTERPRETATION CTC is a more sensitive test than BE. Our results suggest that CTC should be the preferred radiological test for patients with symptoms suggestive of colorectal cancer. FUNDING NIHR Health Technology Assessment Programme, NIHR Biomedical Research Centres funding scheme, Cancer Research UK, EPSRC Multidisciplinary Assessment of Technology Centre for Healthcare, and NIHR Collaborations for Leadership in Applied Health Research and Care.

Natural orifice translumenal endoscopic surgery: critical appraisal of applications in clinical practice

BackgroundNatural orifice translumenal endoscopic surgery (NOTES), with its focus on eliminating incision-related complications, promises to revolutionize the way surgery is performed. This study aimed to summarize the clinical applications of NOTES for humans, outline the techniques used, and discuss the complications and limitations of current techniques.MethodsA literature search was performed using PubMed and Medline search tools to review the extent and outcomes of human procedures undertaken using the NOTES technique in its pure form or as a hybrid procedure reported until July 2008. The end points were the types of operation performed, the approach and technique used for each operation, and the procedure-related complications and technical limitations.ResultsThis review considered 16 publications reporting on 49 human subjects. All the studies except three used hybrid NOTES procedures, with varying amounts of transabdominal assistance. Three transvaginal cholecystectomies, one transvaginal appendectomy, and eight transgastric appendectomies have been performed using a pure NOTES technique. To date, 15 NOTES transvaginal cholecystectomies and 10 NOTES appendectomies (8 transgastric and 2 transvaginal) are reported. Other procedures including peritoneoscopy and sigmoid colectomy are described. Three cases of minor morbidity are reported and no mortality.ConclusionsAlthough initial human results seem encouraging, it is important that this research be conducted in a way that minimizes bad publicity and describes both favorable and adverse outcomes. Robust trials must be conducted at established centers with appropriate experience and institutional board ethical review to allow safe introduction of this novel technique, with adequate and expedient reporting of serious adverse events. The limitations of the current tools and methods are discussed, and suggestions are made for further improvements in the technology to facilitate NOTES operations.

Differences in Inflammatory Bowel Disease Phenotype between South Asians and Northern Europeans Living in North West London, UK

OBJECTIVES:The incidence and prevalence of inflammatory bowel disease (IBD) is increasing throughout Asia. Since the 1950s, there has been substantial migration from South Asia (India, Pakistan, and Bangladesh) to the United Kingdom. The aim of this study was to define the clinical phenotype of IBD in UK South Asians living in North West London, and to compare the results with a white Northern European IBD cohort.METHODS:The phenotypic details of 367 South Asian IBD patients (273 ulcerative colitis (UC) and 94 Crohns disease (CD)), undergoing active follow-up in five North West London hospitals, were compared with those of 403 consecutively collected white Northern European IBD patients (188 UC and 215 CD).RESULTS:The phenotype of IBD differed significantly between the two populations. 63.0% of South Asian UC patients had extensive colitis compared with 42.5% of the Northern European cohort (P<0.0001). Proctitis was uncommon in South Asian UC patients (9.9 vs. 26.1% in Northern European patients, P<0.0001). In the South Asian CD cohort, disease location was predominantly colonic (46.8%). CD behavior differed significantly between the groups, with less penetrating disease compared with Northern Europeans (P=0.01) and a reduced need for surgery (P=0.003).CONCLUSIONS:The phenotype of IBD in South Asians living in North West London is significantly different from that of a white Northern European IBD cohort. Knowledge of ethnic variations in disease phenotype may help to identify key genetic, environmental, and behavioral factors contributing to the development of IBD.