Effects of Thiopurine Withdrawal on Vedolizumab-Treated Patients With Ulcerative Colitis: A Randomized Controlled Trial.

BACKGROUND & AIMS: The impact of thiopurine de-escalation while on vedolizumab versus continuing thiopurine therapy in ulcerative colitis (UC) is unclear. We aimed to determine the effect of thiopurine withdrawal for patients with UC in remission on vedolizumab. METHODS: This multicenter randomized controlled trial recruited UC patients on vedolizumab 300 mg intravenously every 8 weeks and a thiopurine. Patients in steroid-free clinical remission for ≥6 months and endoscopic remission/improvement (Mayo endoscopic subscore ≤1) were randomized 2:1 to withdraw or continue thiopurine. Primary outcome was comparing week 48 vedolizumab trough concentrations. Secondary outcomes were clinical relapse (partial Mayo score ≥3 and fecal calprotectin >150 µg/g or increase in Mayo endoscopic subscore ≥1 from baseline), fecal calprotectin remission (<150 µg/g), C-reactive protein remission (<5 mg/L), centrally read endoscopic remission (Mayo endoscopic subscore = 0), histologic remission (Nancy index = 0), histo-endoscopic remission, and adverse events. RESULTS: In total, 62 patients were randomized to continue (n = 20) or withdraw (n = 42) thiopurine. At week 48, vedolizumab trough concentrations were not significantly different between continue and withdrawal groups (14.7 µg/mL, interquartile rate [IQR], 12.3-18.5 µg/mL versus 15.9 µg/mL, IQR, 10.1-22.7 µg/mL, respectively, P = 0.36). The continue group had significantly higher fecal calprotectin remission (95.0%, 19/20 versus 71.4%, 30/42; P = .03), histologic remission (80.0%, 16/20 versus 48.6%, 18/37; P = .02), and histo-endoscopic remission (75.0%, 15/20 versus 32.4%, 12/37; P = .002) than the withdrawal group. Histologic activity (hazard ratio [HR], 15.5; 95% confidence interval [CI], 1.6-146.5; P = .02) and prior anti-tumor necrosis factor exposure (HR, 6.5; 95% CI, 1.3-33.8; P = .03) predicted clinical relapse after thiopurine withdrawal. CONCLUSIONS: Thiopurine withdrawal did not affect vedolizumab trough concentrations. However, it may increase fecal calprotectin, histologic, and histo-endoscopic activity. Histologic activity and prior anti-tumor necrosis factor exposure may predict disease relapse on thiopurine withdrawal for patients using vedolizumab for UC. Australian and New Zealand Trial Registry, number ACTRN12618000812291.

Safety and effectiveness of Janus kinase inhibitors in the management of inflammatory bowel disease following liver transplantation.

BACKGROUND: The management of inflammatory bowel disease (IBD) patients with concurrent liver transplantation is challenging, and data regarding the safety and efficacy of Janus kinase (JAK) inhibitors with anti-rejection medications are required. We report the experience of all liver transplant recipients receiving tofacitinib and/or upadacitinib for IBD across three states in Australia. METHODS: All liver transplant recipients from the Australian states of Victoria, New South Wales and Tasmania who required tofacitinib or upadacitinib for the treatment of IBD were identified using prospectively maintained liver transplant databases. Patients were followed up until medication cessation or last follow up. Clinical safety and efficacy data were collected. RESULTS: Eight patients (median age 30 years) were included, seven of whom received first-line JAK inhibition with tofacitinib. All patients had failed one or more biologic therapies prior to commencing JAK inhibition, including six patients who had failed two or more agents. JAK inhibition was continued for a median of 17 months, with 143 patient-months of combined follow-up. The anti-rejection medication tacrolimus was prescribed in all patients. Overall, seven (88%) patients achieved clinical remission, including all three patients who were switched from tofacitinib to upadacitinib. One patient required colectomy after 1 month of treatment. There were no other cases of serious infection, venous thromboembolism or major adverse cardiovascular events during follow-up. CONCLUSIONS: As the largest case series to-date, these data indicate that combining JAK inhibition with transplant anti-rejection medication may be a safe and clinically effective method of treating IBD in patients with prior biologic failure.

Higher infliximab and adalimumab trough levels are associated with fistula healing in patients with fistulising perianal Crohn's disease.

BACKGROUND: Tumor necrosis factor-alpha inhibitors, including infliximab and adalimumab, are effective medical treatments for perianal fistulising Crohn's disease (CD), but not all patients achieve fistula healing. AIM: To determine the correlation between perianal fistula healing and closure with infliximab and adalimumab trough levels. METHODS: In this multicentre retrospective study conducted across four tertiary inflammatory bowel disease centres in Australia, we identified CD patients with perianal fistulae on maintenance infliximab or adalimumab who had a trough level within twelve weeks of clinical assessment. Data collected included demographics, serum infliximab and adalimumab trough levels (mg/L) within 12 wk before or after their most recent clinical assessment and concomitant medical or surgical therapy. The primary outcome was fistula healing, defined as cessation in fistula drainage. The secondary outcome was fistula closure, defined as healing and closure of all external fistula openings. Differences between patients who did or did not achieve fistula healing were compared using the chi-square test, t test or Mann-Whitney U test. RESULTS: One hundred and fourteen patients (66 infliximab, 48 adalimumab) were included. Forty-eight (72.7%) patients on maintenance infliximab achieved fistula healing and 18 (27.3%) achieved fistula closure. Thirty-seven (77%) patients on maintenance adalimumab achieved fistula healing and 17 (35.4%) achieved fistula closure. Patients who achieved fistula healing had significantly higher infliximab and adalimumab trough levels than patients who did not [infliximab: 6.4 (3.8-9.5) vs 3.0 (0.3-6.2) mg/L, P = 0.003; adalimumab: 9.2 (6.5-12.0) vs 5.4 (2.5-8.3) mg/L, P = 0.004]. For patients on infliximab, fistula healing was associated with lower rates of detectable anti-infliximab antibodies and younger age. For patients on adalimumab, fistula healing was associated with higher rates of combination therapy with an immunomodulator. Serum trough levels for patients with and without fistula closure were not significantly different for infliximab [6.9 (4.3-10.2) vs 5.5 (2.5-8.3) mg/L, P = 0.105] or adalimumab [10.0 (6.6-12.0) vs 7.8 (4.2-10.0) mg/L, P = 0.083]. CONCLUSION: Higher maintenance infliximab and adalimumab trough levels are associated with perianal fistula healing in CD.

Australia IBD Microbiome (AIM) Study: protocol for a multicentre longitudinal prospective cohort study.

INTRODUCTION: Crohn's disease and ulcerative colitis are common chronic idiopathic inflammatory bowel diseases (IBD), which cause considerable morbidity. Although the precise mechanisms of disease remain unclear, evidence implicates a strong multidirectional interplay between diet, environmental factors, genetic determinants/immune perturbations and the gut microbiota. IBD can be brought into remission using a number of medications, which act by suppressing the immune response. However, none of the available medications address any of the underlying potential mechanisms. As we understand more about how the microbiota drives inflammation, much interest has focused on identifying microbial signals/triggers in the search for effective therapeutic targets. We describe the establishment of the Australian IBD Microbiota (AIM) Study, Australia's first longitudinal IBD bioresource, which will identify and correlate longitudinal microbial and metagenomics signals to disease activity as evaluated by validated clinical instruments, patient-reported surveys, as well as biomarkers. The AIM Study will also gather extensive demographic, clinical, lifestyle and dietary data known to influence microbial composition in order to generate a more complete understanding of the interplay between patients with IBD and their microbiota. METHODS: The AIM Study is an Australian multicentre longitudinal prospective cohort study, which will enrol 1000 participants; 500 patients with IBD and 500 healthy controls over a 5-year period. Assessment occurs at 3 monthly intervals over a 24-month period. At each assessment oral and faecal samples are self-collected along with patient-reported outcome measures, with clinical data also collected at baseline, 12 and 24 months. Intestinal tissue will be sampled whenever a colonoscopy is performed. Dietary intake, general health and psychological state will be assessed using validated self-report questionnaires. Samples will undergo metagenomic, transcriptomic, proteomic, metabolomic and culturomic analyses. Omics data will be integrated with clinical data to identify predictive biomarkers of response to therapy, disease behaviour and environmental factors in patients with IBD. ETHICS AND DISSEMINATION: Ethical approval for this study has been obtained from the South Eastern Sydney Local Health District Research Ethics Committee (HREC 2019/ETH11443). Findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12619000911190.

High prevalence of Crohn disease and ulcerative colitis among older people in Sydney.

OBJECTIVES: To determine the age-standardised prevalence of inflammatory bowel disease (IBD) in a metropolitan area of Sydney, with a focus on its prevalence among older people. DESIGN, SETTING: Population-based epidemiological study of people with IBD in the City of Canada Bay, a local government area in the inner west of Sydney, during 1 March 2016 - 10 November 2016. PARTICIPANTS: Patients diagnosed with confirmed IBD according to the Copenhagen or revised Porto criteria. MAIN OUTCOME MEASURES: Crude prevalence of IBD, including Crohn disease and ulcerative colitis; age-standardised prevalence of IBD, based on the World Health Organization standard population; prevalence rates among people aged 65 years or more. RESULTS: The median age of 364 people with IBD was 47 years (IQR, 34-62 years); 185 were women (50.8%). The crude IBD prevalence rate was 414 cases (95% CI, 371-456 cases) per 100 000 population; the age-standardised rate was 348 cases (95% CI, 312-385 cases) per 100 000 population. The age-standardised rate for Crohn disease was 166 cases (95% CI, 141-192 cases) per 100 000 population; for ulcerative colitis, 148 cases (95% CI, 124-171 cases) per 100 000 population. The IBD prevalence rate in people aged 65 years or more was 612 cases (95% CI, 564-660 cases) per 100 000, and for those aged 85 years or more, 891 cases (95% CI, 833-949 cases) per 100 000; for people under 65, the rate was 380 cases (95% CI, 342-418 cases) per 100 000. CONCLUSIONS: We found that the prevalence of confirmed IBD in a metropolitan sample was highest among older people. Challenges for managing older patients with IBD include higher rates of comorbid conditions, polypharmacy, and cognitive decline, and the immunosuppressive nature of standard therapies for IBD.

Medicinal Cannabis for Inflammatory Bowel Disease: A Survey of Perspectives, Experiences, and Current Use in Australian Patients.

Background: Medicinal cannabis (MC) is an increasingly utilized treatment option for various refractory diseases. While robust clinical evidence supporting MC efficacy in inflammatory bowel disease (IBD) is lacking, many IBD patients report using MC to obtain symptomatic relief. Understanding this use and associated outcomes may help inform future clinical trials. Methods: A cross-sectional anonymous online survey was conducted involving Australians with IBD. It examined attitudes and experiences with MC in relation to IBD management. The survey included validated sub-questionnaires assessing quality of life, medication adherence, IBD severity, and functional impairment. Results: A total of 838 responses were obtained. Results showed 25.3% (n = 212) of respondents were current or previous users of MC (18.1% current, 7.2% previous). Half of the current users also consumed cannabis recreationally although less frequently than for medicinal purposes. Cannabis consumption was via smoking (joints 34.2%; water pipe/bongs 14.5%) or as an oral liquid (19.7%) with products obtained from recreational dealers (44.6%), friends/family (26.1%), or self-grown (9.8%). Only 3 respondents reported using legally accessed products. Clinical ratings of IBD severity did not differ according to cannabis use although users reported more hospitalizations, less engagement with specialist services, and lower medication adherence. IBD symptoms reported as positively affected by cannabis included abdominal pain, stress, sleep, cramping, and anxiety. Most users (92.7%) endorsed cannabis as effective in symptom management. Cannabis-using ulcerative colitis patients reported better quality of life than nonusers on some measures. Conclusion: Many patients in Australia are using illicit MC to manage their IBD. Further clinical trials are required to validate, or refute, patient claims around MC efficacy for symptom control in IBD.

Attitudes and Knowledge of Australian Gastroenterologists Around the Use of Medicinal Cannabis for Inflammatory Bowel Disease.

Background: Medicinal cannabis (MC) is being used for symptomatic relief by many patients with inflammatory bowel disease (IBD), often independently of clinical guidance. Such use presents challenges for supporting clinicians. The aim of this study was to determine the current attitudes, knowledge, and experience of gastroenterologists toward patient use of MC for symptom management in IBD. Methods: Australian gastroenterologists (n = 70) and trainees (n = 23) completed an anonymous, 30-item questionnaire, probing their knowledge, attitudes, and experience with MC in managing IBD. Survey data were collected between April and August 2019. Results: Thirty-nine percent of survey respondents reported having patients using MC; however, only a minority supported use of MC in IBD (21%) or expressed a desire to prescribe (28%). Only 6% claimed good understanding of current patient access pathways and only 31% felt comfortable discussing MC with their patients. Some respondents (20%) cited adverse side effects as a reason for not wanting to prescribe, with driving impairment (64%) and impacts on the developing brain (56%) cited as significant concerns. Nonetheless, MC was ranked as less hazardous than corticosteroids, immunomodulators, and biologics by most respondents, and many (53%) were encouraging of patient participation in future clinical trials. Conclusions: Specialist support for the use of MC in IBD patients is relatively low, potentially reflecting the lack of experience and knowledge with MC, uncertain evidence for efficacy, and the often-unorthodox nature of current MC use in patients. This situation may change rapidly with increased familiarity, evidence development, and education around MC prescribing.

Antispasmodic drugs in colonoscopy: a review of their pharmacology, safety and efficacy in improving polyp detection and related outcomes.

Antispasmodic drugs are cheap, effective and generally safe. They may improve outcomes in colonoscopy, however their use has not been consistent or widespread. This manuscript reviews the three most commonly used antispasmodics in colonoscopy, namely, hyoscine butylbromide (and related ammonium compounds), glucagon and peppermint oil. The pharmacology, action and safety of the agents, as well as the evidence for them improving colonoscopic outcomes will be discussed. In addition to polyp detection, other colonoscopic outcome endpoints of interest include cecal and ileal intubation, and patient comfort. The drugs studied were all found to be effective gastrointestinal antispasmodics with good safety profiles. There is insufficient evidence to conclude whether antispasmodics improve cecal intubation rate, predominantly because the baseline rates are already high. Antispasmodics probably have efficacy in reducing cecal intubation time especially in those with marked colonic spasm. Antispasmodics do not offer significant benefit in polyp detection or improving patient comfort during colonoscopy. Future studies should focus on inexperienced colonoscopists as well as those with marked colonic spasm, in whom the greatest benefit seems to lie.

Full-Spectrum Endoscopy Improves Surveillance for Dysplasia in Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Inflammatory bowel diseases (IBDs) increase the risk of colorectal cancer. Surveillance colonoscopy with chromoendoscopy is recommended, but conventional forward-viewing colonoscopy (FVC) detects dysplasia with low levels of sensitivity. Full-spectrum endoscopy (FUSE) incorporates 2 additional lateral cameras to the forward camera of the colonoscope, allowing endoscopists to view behind folds and in blind spots, which might increase dysplasia detection. We compared FUSE vs FVC in the detection of dysplasia in patients with IBDs. METHODS: We performed a prospective, randomized, cross-over, tandem colonoscopy study comparing FVC vs FUSE in 52 subjects with IBD undergoing surveillance for neoplasia in Australia (23 with Crohn's colitis, 29 with ulcerative colitis; median age, 45.0 y; 60% male; mean IBD duration, 16.4 y). All subjects met national IBD surveillance inclusion criteria; 27 were assigned randomly to groups that underwent FVC followed by FUSE, and 25 were assigned to groups that underwent FUSE followed by FVC. All procedures were performed from February 2014 through December 2015. Random biopsy specimens were collected and visible lesions were collected; all were analyzed histologically. The primary end point was dysplasia missed by the first colonoscopy detected by the second colonoscopy. Dysplasia was diagnosed by an expert gastrointestinal pathologist blinded to the colonoscope allocation in consensus with a second expert pathologist. RESULTS: FVC missed 71.4% of dysplastic lesions per lesion whereas FUSE missed 25.0% per lesion (P = .0001); FVC missed 75.0% of dysplastic lesions per subject and FUSE missed 25.0% per subject (P = .046). FUSE identified a mean of 0.37 dysplastic lesions and FVC identified a mean of 0.13 dysplastic lesions (P = .044). The total colonoscopy times were similar (21.2 min for FUSE vs 19.1 min for FVC; P = .32), but withdrawal time was significantly longer for FUSE (15.8 min) than for FVC (12.0 min) (P = .03). Correcting for per-unit withdrawal time, the mean dysplasia miss rate per subject was significantly lower for FUSE (0.19) than for FVC (0.83; P < .0001). Targeted tissue acquisition identified significantly more dysplastic lesions than random biopsies (P < .0001). CONCLUSIONS: In a prospective cross-over study of IBD patients undergoing surveillance colonoscopy, we found panoramic views obtained by full-spectrum endoscopy increased the number of dysplastic lesions detected, compared with conventional forward-viewing colonoscopy. Trial no: ACTRN12616000047493.

Epidemiology and outcomes of primary sclerosing cholangitis with and without inflammatory bowel disease in an Australian cohort.

BACKGROUND & AIMS: Epidemiological data on primary sclerosing cholangitis (PSC) outside the Northern hemisphere are limited. Similarly, the impact of inflammatory bowel disease (IBD) on PSC outcomes remains unclear. We aimed to study the epidemiology and outcomes of PSC patients with and without IBD in an Australian cohort. METHODS: We retrospectively studied PSC patients attending two tertiary referral hospitals over 20 years. Diagnosis of PSC was made according to international guidelines by positive cholangiography and/or liver biopsy (for small duct PSC) with supporting clinical and laboratory evidence. RESULTS: Of 208 PSC patients (61% male) were studied (2271patient-years follow-up). The median age of PSC diagnosis was similar for PSC-IBD and PSC-only patients (40 years vs 42 years, P = .35). All 33 deaths occurred in PSC-IBD patients while there were no deaths in PSC-only patients (21% vs 0%, P < .01). However, there were no significant differences in liver transplantation (PSC-only 25% vs PSC-IBD 31%, P = .45) and transplant-free survival between PSC-only and PSC-IBD patients (P = .43). On multivariate Cox regression, only elevated international normalized ratio (INR) was associated with a greater risk of death or liver transplant (HR 2.0, 95% CI 1.1-3.6, P = .02). Development of gastrointestinal malignancy was higher in the PSC-IBD group compared to PSC-only group (22% vs 2%, P < .01). CONCLUSION: Australian PSC patients have similar characteristics compared to European and North American cohorts. IBD is a significant predictor of gastrointestinal malignancies. Deaths were more common in PSC-IBD but overall transplant-free survival remained similar in PSC-IBD and PSC-only groups. An elevated INR was an independent predictor of death or liver transplantation.

Validation of the Asia Pacific Colorectal Screening (APCS) score in a Western population: An alternative screening tool.

BACKGROUND AND AIM: Colorectal cancer (CRC) screening is based on colonoscopy or fecal occult blood tests, but is imperfect and costly. The Asia Pacific Colorectal Screening Score (APCS) is derived from age, sex, family history of CRC, and smoking history and has been validated in Asian populations. Validation in a Western population is, however, yet to be tested. METHODS: In a teaching hospital, patients underwent colonoscopy for standard indications and screening over 18 months. Data was collected on age, sex, family history of CRC, smoking, weight, ethnicity, and symptoms. Evaluation of the APCS to predict colonoscopy findings (polyps, adenoma, high risk adenoma, and CRC) was performed. RESULTS: A total of 645 patients were prospectively recruited (46.7% male, median age 57 years); 17.8% were average risk (AR), 50.9% were moderate risk (MR), and 31.3% high risk (HR) on APCS. High risk adenomas (AA) were seen in 14.9% of the HR, 5.2% MR, and 0.9% LR patients, P < 0.0001. Comparing HR and MR to AR patients demonstrated significantly elevated relative risk (RR) for AA: 17.1 (95% confidence interval [CI] 2.4-123; P = 0.0001), and adenoma 6.0 (0.80-44.3; P = 0.044). Comparing HR to MR groups for AA, the RR was 2.87 (1.62-5.06; P = 0.0001). Symptoms did not predict findings (odds ratio [OR]: 1.06 [0.75-1.48]; P = 0.75). Body mass index (BMI) <20 kg/m(2) was protective against colonic polyps (OR: 0.28, 95%CI: 0.11-0.74; P = 0.010), adenoma (0.08, 0.01-0.62; P = 0.015), and AA (perfect prediction, OR 2.35 × 10(-8)). CONCLUSIONS: APCS predicts colonic findings in a Western population, to a greater extent than in Asians, independent to symptoms. Low body weight carries a strong protective effect against colonic neoplasia.

Improving the utility of colonoscopy: Recent advances in practice.

Colonoscopy is a frequently performed diagnostic and therapeutic test and the primary screening tool in several nationalized bowel cancer screening programs. There has been a considerable focus on maximizing the utility of colonoscopy. This has occurred in four key areas: Optimizing patient selection to reduce unnecessary or low yield colonoscopy has offered cost-benefit improvements in population screening. Improving quality assurance, through the development of widely accepted quality metrics for use in individual practice and the research setting, has offered measurable improvements in colonoscopic yield. Significant improvements have been demonstrated in colonoscopic technique, from the administration of preparation to the techniques employed during withdrawal of the colonoscope. Improved techniques to avoid post-procedural complications have also been developed-further maximizing the utility of colonoscopy. The aim of this review is to summarize the recent evidence-based advances in colonoscopic practice that contribute to the optimal practice of colonoscopy.

Knowledge and predictors of dysplasia surveillance performance in inflammatory bowel diseases in Australia.

BACKGROUND: Dysplasia surveillance is recognized as an integral component in the management of inflammatory bowel diseases (IBDs). The adherence to surveillance guidelines is variable, and understanding of quality indicators and predictors of behavior is currently limited. OBJECTIVE: To perform a nationwide evaluation of the quality of IBD surveillance practiced by Australian endoscopists and to determine the predictors of quality practice. DESIGN: Cross-sectional nationwide survey. SETTING: Survey distributed through the gastroenterology and colorectal surgery societies covering knowledge and practice of IBD surveillance. MAIN OUTCOME MEASUREMENTS: Adherence to indicators of high-quality surveillance and median score of IBD surveillance guideline knowledge. RESULTS: A total of 264 responses were received, comprising 240 respondents who perform surveillance screening (218 gastroenterologists, 46 colorectal surgeons). Gastroenterologists were significantly more likely to undertake surveillance (P < .001), adhere to guidelines (P = .02), use advanced imaging modalities (P = .04), and have greater surveillance knowledge than colorectal surgeons (P < .001). Knowledge score and gastroenterologists were independent predictors of dysplasia screening (odds ratio [OR] 1.66; 95% confidence interval [CI], 1.41-1.96 and OR 11.2; 95% CI, 4.53-27.87), guideline adherence (OR 1.15; 95% CI, 1.01-1.31 and OR 2.42; 95% CI, 1.11-5.30), and advanced endoscopic imaging technique use (OR 1.19; 95% CI, 1.05-1.35 and OR 2.2; 95% CI, 1.02-4.74). LIMITATIONS: Potential responder bias results appear, however, aligned with those of previous studies. CONCLUSIONS: IBD dysplasia surveillance in Australia is being performed at a high standard. Gastroenterology specialization and knowledge score have been demonstrated to be strong predictors of high-quality surveillance practice. This is the first study to determine predictors of screening behavior and quantify surveillance quality. These results further emphasize that gastroenterologists should play a key role in IBD surveillance.

Longer duration of transient elastography predicts unreliable liver stiffness measurements.

BACKGROUND: Transient elastography (TE) is a noninvasive, validated method to assess liver fibrosis by obtaining liver stiffness measurements (LSM). However, TE can be limited by unreliable measurement (UM). The relationship between the time taken to perform TE (duration) and UM has not been studied. OBJECTIVES: To determine whether the duration of TE correlates with UM. MATERIALS AND METHODS: We prospectively studied the frequency and predictors of UM over a 5-year period. UM was defined as follows: less than 10 successful measurements, success rate less than 60%, or interquartile range more than 30% of the median LSM value (IQR/LSM>30%). RESULTS: Among the 2834 patients with LSM analysed, UM occurred in 19.0%. Duration [odds ratio (OR) 4.2, 95% confidence interval (CI) 2.8-6.4; P<0.0001] was the strongest predictor of UM, followed by BMI more than 28 kg/m (OR 2.1, 95% CI 1.5-3.0; P<0.0001), age more than 52 (OR 1.6, 95% CI 1.1-2.3; P=0.007) and non-HBV aetiology (OR 1.6, 95% CI 1.1-2.3; P=0.02). An optimal cut-off of 3 min 47 s was calculated for predicting UM (sensitivity 70%, specificity 65%, OR 4.2, 95% CI 2.7-6.6, P<0.0001). Examinations that took longer than 8 min 10 s had a 90% chance of UM. CONCLUSION: In experienced hands, duration is a strong predictor of UM in patients undergoing TE. Examinations longer than 4 min are more likely to be unreliable. Examinations longer than 8 min are unlikely to yield a valid result and should be considered a futility endpoint. Older age and increased BMI and nonhepatitis B aetiology are independent, albeit weaker, predictors of UM.

Association between the ulcerative colitis endoscopic index of severity (UCEIS) and outcomes in acute severe ulcerative colitis.

BACKGROUND: The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) accounts for 86% of the variance between observers in the overall assessment of endoscopic severity, but has not been correlated with outcomes. METHODS: Consecutive cases of acute severe colitis (ASC) defined by Truelove and Witts (TW) criteria were retrospectively evaluated. Demographic details, number of TW criteria, prior medical therapy, UCEIS and inpatient medical therapy were recorded. Pre-specified (adverse) endpoints included rescue therapy, colectomy and readmission. RESULTS: Eighty-nine patients, 48 (54%) male, mean age 38 years, all received intravenous hydrocortisone 400mg/d (median 5 days [range 1-11]). Median follow-up was 14 months (2-33). Forty-eight (54%) were diagnosed the year prior to or at the time of admission. Thirty-six (40%) required rescue therapy (infliximab 25/36, ciclosporin 12/36, one receiving both). Twenty-one (24%) underwent colectomy on the index admission (9/21) or during follow-up (12/21). Median UCEIS score (possible range 0-8) was 5 (3-8). UCEIS was higher in patients requiring rescue therapy or colectomy (median score 6 [range 4-8] versus 5/8 [3-8], both p < 0.005). For UCEIS ≥5, 27/54 (50%) required rescue therapy, compared with 9/33 (27%) for UCEIS ≤4 (p = 0.037). When UCEIS was ≥5, 18/54 (33%) came to colectomy during follow-up, compared with 3/33 (9%) with UCEIS ≤4. Of 14 patients with UCEIS 7 or 8, 11/14 needed rescue therapy and 13/14 met any adverse endpoint. CONCLUSION: Endoscopic severity is associated with a worse outcome in ASC. When the UCEIS is ≥7 on admission, almost all patients will need treatment with infliximab or ciclosporin beyond steroids. This may mark a threshold for an early decision to use infliximab or ciclosporin.

Outcomes of single-dose peri-procedural antibiotic prophylaxis for endoscopic ultrasound-guided fine-needle aspiration of pancreatic cystic lesions.

BACKGROUND: Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is a technique frequently used to diagnose solid and cystic lesions of the pancreas. Antibiotic prophylaxis has been recommended for EUS-FNA of pancreatic cystic lesions but is not universally observed. The most effective antibiotic and the most efficacious route and regimen of administration are also unknown. OBJECTIVE: This cohort study was undertaken to evaluate whether single-dose piperacillin/tazobactam or ciprofloxacin given at the time of the procedure effectively prevents major adverse events and to audit the adherence to this protocol in the setting of EUS-FNA of pancreatic cystic lesions. DESIGN: Consecutive EUS-FNA procedures of pancreatic cystic lesions were performed at Concord Hospital and significant variables regarding the procedure and adverse events were recorded. Patients were also contacted by telephone to follow-up any subacute adverse events they may have experienced. PATIENTS: Over a 30 month period (January 2010-July 2012), a total of 85 EUS-FNAs of pancreatic cysts were performed on 80 different patients. The mean age was 63.2 years (range 17-89 years; 58% females). INTERVENTIONS: Single-dose piperacillin/tazobactam IVs was administered to 87% of patients, while 12% of patients received ciprofloxacin IVs. RESULTS: No patients developed cyst infection, fever, or sepsis (0%) and one patient (1.2%) was hospitalised for self-limited nausea without adverse sequelae. CONCLUSIONS: Single-dose piperacillin/tazobactam at the time of EUS-FNA of pancreatic cysts is an effective prophylaxis of cyst infection or sepsis and can be conveniently given as a single-dose peri-procedurally without further oral antibiotics.

Postpolypectomy haemorrhage following removal of large polyps using mechanical haemostasis or epinephrine: a meta-analysis.

BACKGROUND AND AIM: Postpolypectomy haemorrhage (PPH) is a known adverse event that can occur following polypectomy, occurring in 0.3-6.1% of cases. Previous meta-analysis has included small polyps, which are less likely to bleed, and less amenable to some methods of mechanical haemostasis. No comprehensive cost-benefit analysis of this topic is available. The aim of this study was to perform a meta-analysis of randomized trials and a cost-benefit analysis of prophylactic haemostasis in PPH. METHODS: A total of 3092 abstracts from prospective trials conducted in human colonoscopic polypectomy were screened. Outpatients undergoing polypectomy in seven suitable studies (1426 episodes), without polyposis syndromes or bleeding diathesis, were identified. The interventions of prophylactic haemostatic measures (clips, loops, and/or adrenaline injection) to prevent PPH were assessed. The main outcome measurements were PPH measured by haematochezia or drop in haematocrit >10% or haemoglobin >1 g/dl. Risk ratio and number needed to treat (NNT) were generated using meta-analysis. RESULTS: Comparing any prophylactic haemostasis to none, the pooled risk ratio for PPH was 0.35 (0.21-0.57; p < 0.0001), NNT was 13.6, and cost to prevent one PPH was USD652. Using adrenaline alone vs. no prophylactic haemostasis revealed a pooled risk ratio of 0.37 (0.20-0.66; p = 0.001), NNT 14.0, cost to prevent one PPH USD382. Any prophylactic mechanical haemostasis compared to adrenaline produced a RR for PPH of 0.28 (0.14-0.57; p < 0.0001), NNT 12.3, and cost to prevent one PPH USD1368. CONCLUSIONS: Adrenaline injection or mechanical haemostasis reduces the risk of PPH. Routine prophylactic measures to reduce PPH for polyps larger than 10 mm are potentially cost effective, although more thorough cost-benefit modelling is required.