Gastric intestinal metaplasia: Prevalence in a large Australian center and nationwide survey of endoscopic practice.

Background and Aim: Atrophic gastritis (AG) and gastric intestinal metaplasia (GIM) are early changes in the stepwise progression to gastric adenocarcinoma. There is heterogeneity in international guidelines regarding the endoscopic diagnosis and surveillance of AG and GIM. This study aims to determine the prevalence of GIM in an Australian center and assess the approach of Australian endoscopists for these two conditions. Methods: We conducted a single-center retrospective study of adult patients between January 2015 and December 2020 diagnosed with GIM on gastric biopsy following upper gastric endoscopy. A web-based, 25-question, investigator-designed, multiple-choice survey was distributed among all registered endoscopists in Australia. Results: The overall prevalence of GIM within a single Australian center was 11.7% over 5 years. Of the 1026 patients identified, only 58.7% underwent mapping biopsies using the modified Sydney protocol. Among the cohort, 1.6% had low-grade dysplasia, 0.9% had high-grade dysplasia, and 1.8% had malignancy on initial gastroscopy. Two hundred and sixty-seven (7.2%) endoscopists completed the survey, 44.2% indicated they would perform mapping for all patients, and 36% only for high-risk patients. Only 1.5% (n = 4) of respondents were able to correctly identify all six endoscopic photos of GIM/AG. Conclusion: This study demonstrates that in a large tertiary center, GIM is a prevalent endoscopic finding, but the associated rates of dysplasia and cancer were low. Additionally, among a small proportion of surveyed Australian endoscopists, there is notable variability in the endoscopic approach for AG and GIM and significant knowledge gaps. More training is required to increase the recognition of GIM and compliance with histological mapping.

Surveillance MRI is associated with improved survival in patients with primary sclerosing cholangitis.

BACKGROUND: The benefits of regular surveillance imaging for cholangiocarcinoma in patients with primary sclerosing cholangitis (PSC) are unclear. Hence, we aimed to evaluate the impact of regular magnetic resonance cholangiopancreatography (MRCP) on outcomes of patients with PSC in Australia, where the practice of MRCP surveillance is variable. METHODS: The relationship between MRCP surveillance and survival outcomes was assessed in a multicenter, retrospective cohort of patients with PSC from 9 tertiary liver centers in Australia. An inverse probability of treatment weighting approach was used to balance groups across potentially confounding covariates. RESULTS: A total of 298 patients with PSC with 2117 person-years of follow-up were included. Two hundred and twenty patients (73.8%) had undergone MRCP surveillance. Regular surveillance was associated with a 71% reduced risk of death on multivariate weighted Cox analysis (HR: 0.29, 95% CI: 0.14-0.59, p < 0.001) and increased likelihood of having earlier endoscopic retrograde cholangiopancreatography from the date of PSC diagnosis in patients with a dominant stricture (p < 0.001). However, survival posthepatobiliary cancer diagnosis was not significantly different between both groups (p = 0.74). Patients who had surveillance of less than 1 scan a year (n = 41) had comparable survival (HR: 0.46, 95% CI 0.16-1.35, p = 0.16) compared to patients who had surveillance at least yearly (n = 172). CONCLUSIONS: In this multicenter cohort study that employed inverse probability of treatment weighting to minimize selection bias, regular MRCP was associated with improved overall survival in patients with PSC; however, there was no difference in survival after hepatobiliary cancer diagnosis. Further prospective studies are needed to confirm the benefits of regular MRCP and optimal imaging interval in patients with PSC.

Clinical outcomes of hepatocellular carcinoma surveillance in Melbourne, Australia.

BACKGROUND: Ultrasound surveillance for hepatocellular carcinoma (HCC) may improve early tumour detection but may additionally result in surveillance-related harm through increased evaluation of non-HCC lesions. The incidence of these outcomes has not been reported outside North America. AIMS: We aimed to report the outcomes of HCC surveillance with respect to both surveillance-related benefits and harms. METHODS: We reviewed all HCC surveillance ultrasounds at a large Victorian tertiary hospital network in 2017 and followed their outcomes until 2021. Surveillance-related benefits were defined as early-stage HCC detection. Surveillance-related harm was defined as contrast imaging, biopsies or surgery performed to evaluate non-HCC liver lesions or false-positive alpha-fetoprotein levels. RESULTS: Five hundred and fifty-three patients were included (mean age 54.5 ± 12.3 years, males 67.5%, cirrhosis 50.3%). The most common liver disease aetiology was hepatitis B (53.9%). Over a median of 4.7 years follow-up, early-stage HCC was detected in 3.3% (5.4% in cirrhotic vs 1.1% in non-cirrhotic patients, P < 0.01). 75% of all HCCs were early-stage. Surveillance-related harm occurred in 12.5% (15.5% in cirrhotic vs 9.5% in non-cirrhotic patients, P < 0.04), although most harm was mild (12.1%). In subgroup analysis, the detection of early-stage HCC ranged between 0% (screened outside of guideline criteria and alcoholic cirrhotic patients) and 7.2% (hepatitis C cirrhosis). Harm occurred between 9% (non-cirrhotic hepatitis B) and 20.8% (thrombocytopenia). CONCLUSION: In our study, HCC surveillance was associated with early tumour detection, although many patients experienced mild surveillance-related harm. Novel surveillance strategies and pathways are required to improve detection in high-risk patients and minimise harm in low-risk patients.

Identifying the real-world challenges of dysplasia surveillance in inflammatory bowel disease: a retrospective cohort study in a tertiary health network.

BACKGROUND: Dysplasia surveillance in inflammatory bowel disease (IBD) is often suboptimal and deviates from guidelines. AIMS: To assess dysplasia surveillance behaviours and adherence to guidelines amongst a large tertiary teaching health network with a specialised IBD unit to identify areas where dysplasia surveillance could be improved. METHODS: A retrospective audit of IBD surveillance colonoscopy practice over an 18-month period was performed using the Provation Endoscopy Database and the hospital's primary sclerosing cholangitis database. RESULTS: The audit identified 115 dysplasia surveillance colonoscopies. A total of 37% of index dysplasia colonoscopies were outside recommended guidelines. A total of 10% had inadequate bowel preparation and only 40% had excellent bowel preparation. A total of 28% of patients underwent dye-based chromoendoscopy and 69% underwent high-definition white-light endoscopy. Dye chromoendoscopy was more likely to be used by IBD specialists than interventional endoscopists (P = 0.008) and other endoscopists (P = 0.004). Only IBD specialists and interventional endoscopists used dye chromoendoscopy. Dysplasia or colorectal cancer was detected in 3.4% of the colonoscopies. Overall, the several dysplasia examinations were lower than expected. CONCLUSIONS: Dysplasia surveillance in the IBD population remains an area of improvement given the current national guidelines. IBD specialists are more likely to perform dye chromoendoscopy than other endoscopists/gastroenterologists. Dysplasia rates in this real-world contemporary setting are less than expected in historical studies and may represent improvements in IBD management principles and medications.

Hepatocellular carcinoma surveillance in Australia: current and future perspectives.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and is increasing in incidence in Australia. For most people with cirrhosis and chronic hepatitis B, HCC screening and surveillance is recommended with 6-monthly ultrasound. However, most patients with HCC are still diagnosed outside of surveillance with incurable disease. While HCC surveillance almost certainly reduces cancer-related mortality, the potential harms of surveillance are incompletely understood. Surveillance uptake remains suboptimal in many contexts, and stems from a combination of patient, clinician and system level barriers. Improved case-finding strategies may be required to identify high risk individuals in need of surveillance, as cirrhosis and viral hepatitis are often asymptomatic. HCC prediction models and novel surveillance tools such as biomarker panels, computed tomography and magnetic resonance imaging may have a future role in personalised HCC surveillance. Analyses suggest surveillance may be cost-effective, but Australian data remain limited. A centralised HCC surveillance program may ultimately have a role in delivering improved and more equitable care.

Hepatocellular carcinoma surveillance in the telehealth era: A single-centre review.

BACKGROUND: Real-world hepatocellular carcinoma (HCC) surveillance uptake remains suboptimal, despite evidence that surveillance is associated with lower cancer-related mortality in patients with cirrhosis and chronic hepatitis B. We aimed to examine the impact of telehealth consultations on HCC surveillance rates within a specialist liver clinic. METHODS: We conducted a retrospective observational study within an Australian outreach liver clinic within a culturally diverse community, comparing standard consultations before the COVID-19 pandemic to telehealth consultations during the pandemic. The primary outcome was surveillance uptake defined as the percentage of time up-to-date with surveillance (PTUDS) with the 6-month interval following each scan considered up-to-date. RESULTS: Over 18 months of follow-up for each cohort, the median PTUDS was 86.5% in the standard consultation cohort and 85.5% in the telehealth consultation cohort (p = 0.12). HCC diagnoses did not differ between groups and hospitalisation and mortality rates were low. Using multivariate regression, increasing age, the need for an interpreter and being born in South-East Asia independently predicted PTUDS in the standard consultation cohort, whereas being born in Australia or New Zealand was predictive of a lower PTUDS. Current alcohol use and distance from the clinic predicted a lower PTUDS in the telehealth consultation cohort. In both groups, missed clinic attendances were strongly predictive of a lower PTUDS. CONCLUSION: Telehealth hepatology consultations effectively coordinate HCC surveillance and are associated with similar outcomes to standard consultations. Its implementation should be widely considered given its advantages with regards to accessibility for patients.

High incidence of inflammatory bowel disease in Northern Australia: a prospective community population-based Australian incidence study in the Mackay-Isaac-Whitsunday region.

BACKGROUND AND AIMS: To determine the incidence of inflammatory bowel disease (IBD) in the Mackay-Isaac-Whitsunday region in Northern Queensland (-21.14° S) and to allow a comparison with Southern Australian and New Zealand data (Geelong, Australia -38.14° S; Tasmania -41.43° S and -42.88° S (Launceston and Hobart) and Canterbury, New Zealand -43.46 °S). DESIGN: A prospective observational community population-based IBD study was conducted between 1 June 2017 and 31 May 2018. OUTCOME MEASURES: Primary includes the crude annual incidence rate of IBD, Crohn's disease (CD), ulcerative colitis (UC) and inflammatory bowel disease-unclassified (IBDU), while secondary includes disease phenotype and behaviour. RESULTS: Fifty-six new cases of IBD were identified. Twenty-three were CD, 30 were UC and 3 were IBDU. The crude annual incidence rate per 100 000 for IBD, CD, UC and IBDU were 32.2 (95% confidence interval (CI): 24.78-41.84), 13.23 (95% CI: 8.79-19.90), 17.25 (95% CI: 12.06-24.67) and 1.73 (95% CI: 0.56-5.35). When directly age-standardised to the World Health Organisation Standard Population Distribution, the overall CD, UC and IBDU incidence were 13.19, 17.34 and 1.85 per 100 000, with an overall age-standardised IBD incidence of 32.38. CONCLUSIONS: This is the first study to define the incidence of IBD in a Northern Australian cohort and to allow a comparison between North and Southern Australia. The IBD crude is the highest reported in Australia. Like others, we found a high and low incidence of upper gastrointestinal Crohn's disease and complicated disease at diagnosis respectively, likely reflective of the increased availability and early uptake of endoscopic procedures.

Preconception, antenatal and postpartum management of inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD), comprising ulcerative colitis and Crohn's disease, commonly affects individuals of childbearing age. Pregnancy in women with IBD presents an anxiety-provoking prospect for practitioners and patients alike, with disease flares occurring in between 20% and 55% of patients antenatally. OBJECTIVE: The aim of this review is to provide an overview of antenatal IBD management principles and therapeutic goals, with a specific focus on the role of general practitioners. DISCUSSION: A collaborative approach is favoured in managing pregnancy and IBD. Preconception counselling should be prioritised, with emphasis on the importance of achieving three months of preconception corticosteroid-free remission. Close monitoring of disease activity in pregnancy is crucial, warranting the careful interpretation of both clinical and biochemical parameters. Reassurance regarding the safety of IBD medications in pregnancy and vaginal delivery can be provided in the majority of cases. Specialist support should be sought expeditiously in the setting of disease flare, particularly where symptoms and biochemical parameters are refractory to escalation of 5-aminosalicylates or topical therapies, corticosteroids or biologic agents are required, or an emergent IBD complication is suspected.

Lenvatinib for the treatment of hepatocellular carcinoma-a real-world multicenter Australian cohort study.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a serious complication of chronic liver disease. Lenvatinib is an oral multikinase inhibitor registered to treat advanced HCC. This study evaluates the real-world experience with lenvatinib in Australia. METHODS: We conducted a retrospective cohort study of patients treated with lenvatinib for advanced HCC between July 2018 and November 2020 at 11 Australian tertiary care hospitals. Baseline demographic data, tumor characteristics, lenvatinib dosing, adverse events (AEs) and clinical outcomes were collected. Overall survival (OS) was the primary outcome. Progression free survival (PFS) and AEs were secondary outcomes. RESULTS: A total of 155 patients were included and were predominantly male (90.7%) with a median age of 65 years (interquartile range [IQR]: 59-75). The main causes of chronic liver disease were hepatitis C infection (40.0%) and alcohol-related liver disease (34.2). Median OS and PFS were 7.7 (95% confidence interval [CI]: 5.8-14.0) and 5.3 months (95% CI: 2.8-9.2) respectively. Multivariate predictors of mortality were the need for dose reduction due to AEs (Hazard ratio [HR] 0.41, p < 0.01), new or worsening hypertension (HR 0.42, p < 0.01), diarrhoea (HR 0.47, p = 0.04) and more advanced BCLC stage (HR 2.50, p = 0.04). Multivariable predictors of disease progression were higher Child-Pugh score (HR 1.25, p = 0.04), the need for a dose reduction (HR 0.45, p < 0.01) and age (HR 0.96, p < 0.001). AEs occurred in 83.9% of patients with most being mild (71.6%). CONCLUSIONS: Lenvatinib remains safe and effective in real-world use. Treatment emergent diarrhoea and hypertension, and the need for dose reduction appear to predict better OS.

Timing of Live Attenuated Vaccination in Infants Exposed to Infliximab or Adalimumab in Utero: A Prospective Cohort Study in 107 Children.

BACKGROUND AND AIMS: For infants exposed in utero to anti-tumour necrosis factor-α [TNF] medications, it is advised that live-attenuated vaccinations be postponed until the drug is cleared, but little is known about time to clearance. To minimize delays before live-attenuated vaccination can be given, we aimed to develop a pharmacokinetic model to predict time-to-clearance in infants exposed during pregnancy. METHODS: We prospectively followed in utero infliximab/adalimumab-exposed infants of mothers with inflammatory bowel disease across four countries between 2011 and 2018. Infants with a detectable anti-TNF umbilical-cord level and at least one other blood sample during the first year of life were included. RESULTS: Overall, 107 infants were enrolled, including 166 blood samples from 71 infliximab-exposed infants and 77 samples from 36 adalimumab-exposed infants. Anti-TNF was detectable in 23% [n = 25] of infants at 6 months. At 12 months, adalimumab was not detected but 4% [n = 3] had detectable infliximab. A Bayesian forecasting method was developed using a one-compartment pharmacokinetic model. Model validation showed that the predicted clearing time was in accordance with the measured observations. A clinician-friendly online calculator was developed for calculating full anti-TNF clearing time: https://xiaozhu.shinyapps.io/antiTNFcalculator2/. CONCLUSIONS: Almost one-quarter of infants born to mothers receiving anti-TNF during pregnancy have detectable anti-TNF at 6 months. To limit the time to live-attenuated vaccination in infants of mothers receiving anti-TNF during pregnancy, the results of a cord drug level at birth and a second sample ≥ 1 month thereafter can be used to estimate the time for full anti-TNF clearance in these children.

Intensive drug therapy versus standard drug therapy for symptomatic intestinal Crohn's disease strictures (STRIDENT): an open-label, single-centre, randomised controlled trial.

BACKGROUND: Strictures are the most common structural complication of Crohn's disease. Surgery and endoscopic balloon dilation are the main treatments; drug therapy has been considered contraindicated. Given that most strictures have an inflammatory component, we aimed to find out whether strictures are responsive to drug treatment and whether intensive drug therapy is more effective than standard drug therapy. METHODS: This open-label, single-centre, randomised controlled trial was performed in one specialist inflammatory bowel disease centre in Australia. Patients aged 18 years or older with Crohn's disease were included. Eligible patients had a de novo or postoperative anastomotic intestinal stricture on MRI or ileocolonoscopy, symptoms consistent with chronic or subacute intestinal obstruction (postprandial abdominal pain in the presence of a confirmed stricture), and evidence of active intestinal inflammation. Patients were randomly assigned (2:1) to receive intensive high-dose adalimumab (160 mg adalimumab once per week for 4 weeks followed by 40 mg every 2 weeks, with escalation of dose at 4 months and 8 months if assessment of disease activity indicated active inflammation) plus thiopurine (initial dose of azathioprine 2·5 mg/kg or mercaptopurine 1·5 mg/kg, with dose adjustment based on thiopurine metabolite testing) or standard adalimumab monotherapy (160 mg at week 0, 80 mg at week 2, then 40 mg every 2 weeks) using stratified fixed block randomisation. Stratification factors were stricture dilation at study baseline colonoscopy and current biologic drug use. The primary endpoint was improvement (decrease) in the 14-day obstructive symptom score at 12 months by one or more points compared with baseline. This trial is registered with ClinicalTrials.gov, NCT03220841, and is completed. FINDINGS: Between Sept 10, 2017, and Sept 6, 2019, 123 patients were screened and 77 randomly assigned to intensive adalimumab plus thiopurine treatment (n=52) or standard adalimumab treatment (n=25). At 12 months, improvement in obstructive symptom score was noted in 41 (79%) of 52 patients in the intensive treatment group and 16 (64%) of 25 in the standard treatment group (odds ratio [OR] 2·10 [95% CI 0·73-6·01]; p=0·17). Treatment failure occurred in five (10%) patients in the intensive treatment group versus seven (28%) in the standard treatment group (OR 0·27 [95% CI 0·08-0·97]; p=0·045); four patients in each group required stricture surgery (0·44 [0·10-1·92]; p=0·27). Crohn's Disease Activity Index was less than 150 in 36 (69%) patients in the intensive treatment group versus 15 (60%) in the standard treatment group (1·50 [0·56-4·05]; p=0·42). MRI at 12 months showed improvement using the stricture MaRIA score (≥25%) in 31 (61%) of 51 versus seven (28%) of 25 patients (3·99 [1·41-11·26]; p=0·0091). MRI complete stricture resolution was seen in ten (20%) versus four (16%) patients (1·28 [0·36 to 4·57]; p=0·70). Intestinal ultrasound at 12 months showed improvement (>25%) in bowel wall thickness in 22 (51%) of 43 versus seven (33%) of 21 patients (2·10 [0·71 to 6·21]; p=0·18). Faecal calprotectin normalised in 32 (62%) versus 11 (44%) patients (2·04 [0·77-5·36]; p=0·15). Normalisation of CRP was seen in 32 (62%) versus 11 (44%) patients (2·04 [0·77-5·36]; p=0·15). Eight (15%) patients in the intensive treatment group and four (16%) in the standard treatment group reported serious adverse events. No deaths occurred during the study. INTERPRETATION: Crohn's disease strictures are responsive to drug treatment. Most patients had improved symptoms and stricture morphology. Treat-to-target therapy intensification resulted in less treatment failure, a reduction in stricture-associated inflammation, and greater improvement in stricture morphology, although these differences were not significantly different from standard therapy. FUNDING: Australian National Health and Medical Research Council, Gastroenterological Society of Australia Ferring IBD Clinician Establishment Award, Australasian Gastro Intestinal Research Foundation, AbbVie, and the Spotlight Foundation.

Clinical outcomes of patients with two small hepatocellular carcinomas.

BACKGROUND: Management of single small hepatocellular carcinoma (HCC) is straightforward with curative outcomes achieved by locoregional therapy or resection. Liver transplantation is often considered for multiple small or single large HCC. Management of two small HCC whether presenting synchronously or sequentially is less clear. AIM: To define the outcomes of patients presenting with two small HCC. METHODS: Retrospective review of HCC databases from multiple institutions of patients with either two synchronous or sequential HCC ≤ 3 cm between January 2000 and March 2018. Primary outcomes were overall survival (OS) and transplant-free survival (TFS). RESULTS: 104 patients were identified (male n = 89). Median age was 63 years (interquartile range 58-67.75) and the most common aetiology of liver disease was hepatitis C (40.4%). 59 (56.7%) had synchronous HCC and 45 (43.3%) had sequential. 36 patients died (34.6%) and 25 were transplanted (24.0%). 1, 3 and 5-year OS was 93.0%, 66.1% and 62.3% and 5-year post-transplant survival was 95.8%. 1, 3 and 5-year TFS was 82.1%, 45.85% and 37.8%. When synchronous and sequential groups were compared, OS (1,3 and 5 year synchronous 91.3%, 63.8%, 61.1%, sequential 95.3%, 69.5%, 64.6%, P = 0.41) was similar but TFS was higher in the sequential group (1,3 and 5 year synchronous 68.5%, 37.3% and 29.7%, sequential 93.2%, 56.6%, 48.5%, P = 0.02) though this difference did not remain during multivariate analysis. CONCLUSION: TFS in patients presenting with two HCC ≤ 3 cm is poor regardless of the timing of the second tumor. All patients presenting with two small HCC should be considered for transplantation.

Long-term outcomes of perianal fistulizing Crohn's disease in the biologic era.

BACKGROUND AND AIM: While the advent of biologic therapy has led to improved outcomes in perianal fistulizing Crohn's disease (pfCD), loss of response is common. Previous studies suggest that patients who achieve radiological healing (with healing of underlying tracts on magnetic resonance imaging [MRI]) have a longer duration of response. The aim of this study was to characterize MRI outcomes of pfCD at a specialist inflammatory bowel disease (IBD) unit and compare the long-term clinical outcomes between patients achieving MRI and clinical healing. METHODS: A retrospective analysis of perianal fistulizing Crohn's patients treated at one specialist IBD unit was performed. Records were reviewed for patient demographics, disease history, clinical assessments, investigation results, and disease flares. Clinical remission was defined as closure of all baseline fistula openings. Radiological healing was defined as the absence of any T2-hyperintense sinuses, tracts, or collections. The primary end-point was rate of MRI healing. The secondary outcome was defined as flare-free period (time between clinical or radiological healing and patients' first signs/symptoms requiring therapy escalation). RESULTS: A total of 93 patients were included, with a median follow-up of 4.8 years (interquartile range, 2.4-6 years). Of 44 patients, 22 (50%) achieved clinical remission, while 15 of 93 (16%) achieved radiological healing. Of 22 patients, 10 (45%) with clinical remission had a subsequent disease flare (median time of 7 months) compared with 3 of 15 (20%) patients with MRI healing (median time of 3.6 years). Radiological healing was associated with a significantly longer flare-free period (P = 0.01). CONCLUSION: Radiological healing occurs less commonly but represents a deeper form of healing, associated with improved long-term clinical outcomes.

Crohn's Colitis Care (CCCare): bespoke cloud-based clinical management software for inflammatory bowel disease.

BACKGROUND: Adherence to evidence-based management is variable in inflammatory bowel disease (IBD), which leads to worse patient outcomes and higher healthcare utilization. Solutions include electronic systems to enhance care, but these have often been limited by lack of clinician design input, poor usability, and low perceived value. A cloud-based IBD-specific clinical management software - 'Crohn's Colitis Care' (CCCare) was developed by Australia and New Zealand Inflammatory Bowel Disease Consortium clinicians and software developers to improve this. METHODS: CCCare captures patient-reported disease activity and medical assessment, medication monitoring, cancer screening, preventative health, and facilitates communication with the IBD team and referring doctor. De-identified longitudinal data are stored separately in a clinical quality registry for research. CCCare was tested for feasibility and usability in routine clinical settings at two large Australian hospitals. Users' experience was evaluated with System Usability Scale (SUS). Value to clinicians and patients was assessed by qualitative feedback. Security was assessed by penetration testing. RESULTS: Users (n = 13; doctors, nurses, patients) reported good usability and learnability (mean SUS score 75 (range 50-95), sub-scores were 77 (50-94) and 68 (38-100), respectively). Patients reported better communication with clinical team and greater ability to track disease. Clinicians highlighted structured management plans, medication adherence, and centralised data repository as positive features. Penetration testing was passed successfully. CONCLUSIONS: Initial evaluation demonstrates CCCare is usable, secure, and valued in clinical use. It is designed to measure outcomes of clinical care, including efficacy, quality, cost, and complications for individuals, and to audit these at hospital and national level.

Vedolizumab for ulcerative colitis: Real world outcomes from a multicenter observational cohort of Australia and Oxford.

BACKGROUND: Vedolizumab (VDZ), a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis (UC) patients. AIM: To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving remission. METHODS: A retrospective review of Australian and Oxford, United Kingdom data for UC patients. Clinical response at 3 mo, endoscopic remission at 6 mo and clinical remission at 3, 6 and 12 mo were assessed. Cox regression models and Kaplan Meier curves were performed to assess the time to remission, time to failure and the covariates influencing them. Safety outcomes were recorded. RESULTS: Three hundred and three UC patients from 14 centres in Australia and United Kingdom, [60% n = 182, anti-TNF naïve] were included. The clinical response was 79% at 3 mo with more Australian patients achieving clinical response compared to Oxford (83% vs 70% P = 0.01). Clinical remission for all patients was 56%, 62% and 60% at 3, 6 and 12 mo respectively. Anti-TNF naive patients were more likely to achieve remission than exposed patients at all the time points (3 mo 66% vs 40% P < 0.001, 6 mo 73% vs 46% P < 0.001, 12 mo 66% vs 51% P = 0.03). More Australian patients achieved endoscopic remission at 6 mo compared to Oxford (69% vs 43% P = 0.01). On multi-variate analysis, anti-TNF naïve patients were 1.8 (95%CI: 1.3-2.3) times more likely to achieve remission than anti-TNF exposed (P < 0.001). 32 patients (11%) had colectomy by 12 mo. CONCLUSION: VDZ was safe and effective with 60% of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome.

Prognostic role of alpha-fetoprotein in patients with hepatocellular carcinoma treated with repeat transarterial chemoembolisation.

BACKGROUND: Repeat transarterial chemoembolisation (rTACE) is often required for hepatocellular carcinoma (HCC) to achieve disease control, however, current practice guidelines regarding treatment allocation vary significantly. This study aims to identify key factors associated with patient survival following rTACE to facilitate treatment allocation and prognostic discussion. METHOD: Patients with HCC undergoing rTACE at six Australian tertiary centers from 2009 to 2014 were included. Variables encompassing clinical, tumour, treatment type and response factors were analysed against the primary outcome of overall survival. Univariate analysis and multivariate Cox regression modelling were used to identify factors pre- and post-TACE therapy significantly associated with survival. RESULTS: Total of 292 consecutive patients underwent rTACE with mainly Child Pugh A cirrhosis (61%) and BCLC stage A (57%) disease. Median overall survival (OS) was 30 months (IQR 15.2-50.2) from initial TACE. On multivariate analysis greater tumour number (p = 0.02), higher serum bilirubin (p = 0.007) post initial TACE, and hepatic decompensation (p = 0.001) post second TACE were associated with reduced survival. Patients with serum AFP ≥ 200 ng/ml following initial TACE had lower survival (p = 0.001), compared to patients with serum AFP level that remained < 200 ng/ml post-initial TACE, with an overall survival of 19.4 months versus 34.7 months (p = 0.0001) respectively. CONCLUSION: Serum AFP level following initial treatment in patients undergoing repeat TACE for HCC is a simple and useful clinical prognostic marker. Moreover, it has the potential to facilitate appropriate patient selection for rTACE particularly when used in conjunction with baseline tumour burden and severity of hepatic dysfunction post-initial TACE.

Accuracy of point-of-care intestinal ultrasound for Crohn's disease.

BACKGROUND: Point-of-care ultrasound (POCUS), performed by a gastroenterologist, provides safe and convenient imaging allowing for immediate clinical decision in Crohn's disease. The minimum training required to gain competency, its accuracy and clinical utility requires evaluation. METHODS: In this pilot study, Crohn's disease activity and extent were assessed using POCUS (performed by a single gastroenterologist following the completion of 200 supervised scans), magnetic resonance enterography (MRE) and ileo-colonoscopy. The presence of complications was assessed by POCUS and MRE. Accuracy of POCUS was analysed with respect to MRE and ileo-colonoscopy. Agreement between modalities was assessed using kappa coefficient. RESULTS: Forty-two patients had a POCUS paired with MRE. Thirty-eight patients had a POCUS paired with ileo-colonoscopy. When compared to MRE, POCUS was accurate in the assessment of disease activity (sensitivity 87.5%, specificity 61.1%, ROC 0.74), extent (sensitivity 77.8%, specificity 83.3%, ROC 0.81) and complications (sensitivity 85.7%, specificity 94.3%, ROC 0.90). Agreement between POCUS and MRE was moderate (kappa estimates 0.50, P < 0.001, 0.61, P < 0.001 and 0.76, P < 0.001) for disease activity, extent and complications, respectively. When compared to ileo-colonoscopy, POCUS was accurate in the assessment of disease activity (sensitivity 72%, specificity 86%, ROC 0.79) and extent (sensitivity 85.7%, specificity 86%, ROC 0.86). For POCUS and ileo-colonoscopy, kappa estimates were 0.55, P < 0.001 for disease activity and 0.62, P < 0.001 for disease extent. CONCLUSION: POCUS performed by a gastroenterologist after completion of limited training is accurate for assessing Crohn's disease activity, extent and the presence of complications.