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Background and Aim: Disease recurs frequently after Crohn's disease resection. The role of serological antimicrobial antibodies in predicting recurrence or as a marker of recurrence has not been well defined., Methods: A total of 169 patients (523 samples) were prospectively studied, with testing peri-operatively, and 6, 12 and 18 months postoperatively. Colonoscopy was performed at 18 months postoperatively. Serologic antibody presence (perinuclear anti-neutrophil cytoplasmic antibody [pANCA], anti-Saccharomyces cerevisiae antibodies [ASCA] IgA/IgG, anti-OmpC, anti-CBir1, anti-A4-Fla2, anti-Fla-X) and titer were tested. Quartile sum score (range 6-24), logistic regression analysis, and correlation with phenotype, smoking status, and endoscopic outcome were assessed., Results: Patients with ≥ 2 previous resections were more likely to be anti-OmpC positive (94% vs 55%, ≥ 2 vs < 2, P = 0.001). Recurrence at 18 months was associated with anti-Fla-X positivity at baseline (49% vs 29%; positive vs negative, P = 0.033) and 12 months (52% vs 31%, P = 0.04). Patients positive (n = 28) for all four antibacterial antibodies (anti-CBir1, anti-OmpC, anti-A4-Fla2, and anti-Fla-X) at baseline were more likely to experience recurrence at 18 months than patients negative (n = 32) for all four antibodies (82% vs 18%, P = 0.034; odds ratio 6.4, 95% confidence interval 1.16-34.9). The baseline quartile sum score for all six antimicrobial antibodies was higher in patients with severe recurrence (Rutgeert's i3-i4) at 18 months, adjusted for clinical risk factors (odds ratio 1.16, 95% confidence interval 1.01-1.34, P = 0.039). Smoking affected antibody status., Conclusions: Anti-Fla-X and presence of all anti-bacterial antibodies identifies patients at higher risk of early postoperative Crohn's disease recurrence. Serologic screening pre-operatively may help identify patients at increased risk of recurrence., (© 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Rectally administered topical agents have demonstrated efficacy in the maintenance of distal colitis (DC) and proctitis and as they are rarely associated with significant blood drug levels, side effects are infrequent. The topical 5-aminosalicylic acid (5-ASA) suppositories and enemas target different regions of the distal colon and are effective for proctitis and DC, respectively. They demonstrate clinical results that are better than oral 5-ASAs and are preferred to topical steroids with better clinical, endoscopic and histological outcomes, without the risk of adrenal suppression. Disease resistant to topical agents, however, can be extremely difficult to manage. The addition of oral 5ASAs, steroids, immunosuppressants and the anti-tumor necrosis factor-α agents may be effective, but can result in significant side effects and not all patients will respond to the therapies. It is for these patients that new and novel therapies are required. Novel topical agents have been proposed for the management of resistant DC. These agents included butyrate, cyclosporine, and nicotine enemas, as well as tacrolimus suppositories, and tacrolimus, ecabet sodium, arsenic, lidocaine, bismuth, rebamipide and thromboxane enemas. While some of these agents appear to demonstrate impressive outcomes, the majority have only been examined in small open-labeled studies. There is thus a desperate need for more randomized double-blinded placebo controlled studies to investigate the clinical utility of these topical therapies. This review summarizes the efficacy of the established topical therapies, and explores the available data on the new and novel topical agents for the management of DC and proctitis., (© 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

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., Methods: Serious infections, defined as 'requiring hospital admission' and TB cases in patients receiving, or within 3 months following, anti-TNF-α therapy were analyzed across Australia and New Zealand. Patient demographics, IBD medications, duration of anti-TNF-α therapy, and infection details were collected., Results: A total of 5562 IBD patients were managed across the centers. Of these, 489 (16.8%) Crohn's disease and 137 (5.2%) ulcerative colitis patients received anti-TNF-α therapy. There were three cases of latent TB that received prophylaxis prior to anti-TNF-α therapy. No cases of active TB were reported. Fourteen (2.2%) serious infections occurred. Seven occurred in patients receiving anti-TNF-α therapy for less than 6 months, including two cases of primary Varicella zoster (VZV), two cases of Pneumocystis jiroveci pneumonia, two cases of Staphylococcus aureus bacteremia, and one severe flu-like illness. Six patients were taking additional immunosuppressive medications. The other seven infections occurred after 6 months (mean 32.6 ± 24.3 months) and included one case of primary VZV, one flu-like illness, and five bacterial infections. All infections resolved with treatment., Conclusion: TB is a very rare complication of anti-TNF-α therapy in Australia and New Zealand. Serious infections are uncommon but early opportunistic infections with Pneumocystis jiroveci pneumonia suggest a need for vigilance in patients on multiple immunosuppressive medications. VZV vaccination prior to immunosuppressive therapy should be considered in VZV-naïve patients., (© 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Background: Anti-tumor necrosis factor (TNF)-alpha medications are effective in Crohn's Disease (CD) and efficacious in ulcerative colitis (UC). Adalimumab has been available through the Australian Pharmaceutical Benefits Scheme since August 2008, but clinical experience for inflammatory bowel disease (IBD) in Australia is limited., Aims: To determine adalimumab efficacy for IBD in the Australian setting., Methods: Crohn's disease or UC/IBD unclassified (UC/IBDU) patients received adalimumab after failure of disease control with conventional therapies or loss of control by infliximab. Response/remission at 8 and 12 weeks were determined by the Crohn's Disease Activity Index (CDAI) and Colitis Activity Index (CAI). All patients received 160 mg (week 0), 80 mg (week 2), followed by 40 mg every-other-week (eow). Patients with a limited response at 8 weeks were considered for weekly adalimumab., Results: Of 38 CD patients 86.8% (33/38) had active luminal and 23.7% (9/38) fistulising disease at inclusion. Response occurred in 81.8% and 84.4% of luminal CD at 8 and 12 weeks, while 54.5% and 63.6% remitted respectively. 77.8% of fistulising CD responded and 55.6% remitted at 12 weeks. Fifteen CD patients had previously lost response to infliximab, and 86.7% of these responded and 53.3% remitted at 12 weeks. Of the seven UC/IBDU patients 43% and 14% responded, while 29% and 0% remitted at 8 and 12 weeks., Conclusion: In CD, adalimumab is as, if not more, effective in the clinical setting than in the trials, and is effective in patients with an attenuated response to infliximab. Its efficacy is not as good in UC, but this requires further clarification.

Background and Aim: The use of infliximab in the treatment of Crohn's disease (CD) is acceptable and appears to be effective in ulcerative colitis (UC). Careful patient selection, resulting in infliximab only for truly refractory inflammatory bowel disease (IBD), may improve its efficacy. The present study aimed to determine if careful patient selection improved infliximab efficacy in IBD., Methods: CD or UC/IBD unclassified patients (Montreal classification) were considered for infliximab treatment only after failure of disease control with conventional therapies and confirmation of active disease. Patients with purely luminal IBD received a single infliximab dose. Patients with fistulizing disease (with or without luminal disease) received infliximab at 0, 2 and 6 weeks. Changes to Harvey Bradshaw (HBI) for inflammatory CD and Colitis Activity Index (CAI) for UC/IBDU were used to determine the response and remission rates. In fistulizing CD, a remission was sustained cessation of drainage and resolution of the fistula. Response was correlated to inflammatory marker levels., Results: Seventy IBD patients were treated. In CD, 85.2% (46/54) had active luminal and 40.7% (22/54) had fistulizing disease. In luminal CD, at 8 weeks a single infliximab dose induced remission in 75% (24/32) of patients compared to 92.9% (13/14) after infliximab at 0, 2 and 6 weeks. Fistulizing disease responded in 77.2% (17/22) and remitted in 50% (11/22) of patients at 8 weeks. In UC/IBDU, 75% (12/16) responded and 43.8% (7/16) of patients were in remission at 8 weeks., Conclusion: Careful patient selection may improve infliximab's efficacy and clinical remission appears greater after induction with three infliximab doses in CD. Clinical efficacy is suggested for UC/IBDU.

Background and Aim: New treatments for Crohn's disease are expensive and place economic strain upon health-care systems, and 'value-for-money' needs to be confirmed. This study aimed to correlate disease severity with health-related quality of life and with health-care resource use, to allow evaluation of the cost effectiveness of these treatments., Methods: A cross-sectional, non-interventional, pharmacoeconomics study was performed with patients completing questionnaires comprising demographic, disease and health-care utilization questions, together with the disease-specific Inflammatory Bowel Disease Questionnaire (IBDQ) and the Assessment of Quality of Life (AQoL) multi-attribute utility instrument. The Crohn's Disease Activity Index (CDAI) was used to assess disease severity., Results: 143 patients with a broad range of disease severity (CDAI 36-446, fistulae 23%) were recruited from referral centers. Stepwise regression analyses demonstrated a negative correlation between disease severity and both IBDQ and AQoL (both P < 0.0001). Age, gender and years since diagnosis did not impact upon either of the quality-of-life outcomes. Mean utility score for non-fistulizing patients with moderate-severe active disease (CDAI >/= 220) was 0.45, mild disease (CDAI 150-219) was 0.68 and for remission (CDAI < 150) was 0.77. Health-care resource utilization increased with increasing CDAI (P < 0.001), with hospital admissions being the largest component cost. Twenty-seven percent of patients (mean age 38 year) received a government benefit, 51% primarily due to their Crohn's disease., Conclusion: Crohn's disease severity correlates with poor quality of life. Utility scores determined will permit cost-utility analyses to be made in order to best allocate limited health resources.

Background and Objectives: Significance of the small colonic polyp is unclear and its removal is frequently determined by the proceduralist's clinical impression. Our aims were to determine if clinical discernment is accurate, and the likelihood that lesions < 10 mm are histologically advanced., Method: We prospectively collected 1988 lesions from 854 subjects (2215 consecutive colonoscopies). Lesion size, location, patient age, sex and the colonoscopist's clinical impression was recorded., Results: Clinical assessment for neoplasia had a sensitivity of 87.4%, specificity of 65.0%, positive predictive value of 76.0% and negative predictive value of 80.2%, resulting in an accuracy of 73.4%. Factors predictive of correct clinical impression were polyp size, location in the rectum and being pedunculated, but not the patient's age, sex or the endoscopist's experience. Of the 1434 lesions < or = 5 mm in size, 44.5% were neoplastic and 3.5% were histologically advanced. Of the 266 lesions 6-9 mm, 79.3% were neoplastic, 19.9% were histologically advanced, five demonstrated high-grade dysplasia and three were malignant. Only two patients with an adenocarcinoma or high-grade dysplasia in a polyp <10 mm had a lesion > or =10 mm elsewhere in the colon. Of the 288 lesions > or =10 mm in size, 92.7% were neoplastic, 29.5% had a villous component, 6.9% demonstrated high-grade dysplasia and 29.2% were malignant. Factors predictive of neoplasia were patient age, polyp size and sessile nature of the lesion., Conclusion: Polyps < 10 mm had a significant risk of neoplasia and advanced histology and, in general, clinical impression correlated poorly with neoplasia. Removal of all lesions proximal to the rectum, regardless of size, should therefore be considered.