Comprehensive review and update of stricturing Crohn's disease.

Up to 50% of patients with Crohn's disease develop a stricture within 10 years of diagnosis. Crohn's strictures can compose of inflammation, fibrosis or smooth muscle expansion and usually a combination of these. There have been numerous new developments in imaging modalities in determining the composition of Crohn's strictures. Magnetic resonance imaging remains the best upfront imaging modality to characterize Crohn's strictures. Gastrointestinal ultrasound (GIUS) has an increasing role in clinical practice, particularly for monitoring stricture response as a treat-to-target tool. Novel imaging techniques to differentiate between fibrosis and inflammatory strictures have been developed including contrast-enhanced GIUS, strain or shear wave elastography with GIUS and multiple new magnetic resonance imaging (MRI) protocols, including diffusion weighted, delayed contrast enhancement and magnetization transfer MR protocols. However, these techniques require further validation and standardization. Regarding therapeutics, anti-tumor necrosis agents with a treat-to-target strategy have the highest quality evidence in treating strictures and can lead to stricture regression in some cases. Endoscopic balloon dilatation remains a mainstay in the treatment algorithm of treating predominantly fibrostenotic Crohn's strictures, particularly those which are symptomatic, < 5 cm in length and not causing prestenotic dilatation. Endoscopic balloon dilatation has greater effectiveness in anastomotic strictures. Surgery remains an important treatment option in Crohn's strictures, with segmental resection and stricturoplasty having their own advantages and disadvantages. Kono-S anastomosis may be superior to conventional anastomosis for endoscopic recurrence; however, further high-quality studies are required to confirm this. Using risk stratification models such as the BACARDI risk model is important to guide management decisions between a medical and surgical approach. Early post-operative medical prophylaxis with an advanced therapy is an important consideration to prevent disease recurrence. This review expands on the above topics, highlights research gaps and provides a suggested investigation and management pathway in stricturing Crohn's disease.

Perceived dietary intolerances, habitual intake and diet quality of patients with an ileoanal pouch: Associations with pouch phenotype (and behaviour).

BACKGROUND AND AIMS: Ileoanal pouch patients frequently attribute pouch-related symptoms and pouchitis with diet. We aimed to assess perceived food intolerance and habitual dietary intake and their relationship with pouch indication, symptoms and current or history of pouchitis. METHODS: In this cross-sectional study, patients with an ileoanal pouch completed a dietary intolerance and a food frequency questionnaire, that specifically quantifies habitual intake of FODMAPs. Perceived dietary intolerance rates, nutrient intake and diet quality, and their differences based on pouch indication, symptom, and current or history of pouchitis were assessed. Associations between intolerances and intake, and between dietary intake with pouchitis risk were analysed using univariable and multivariable regression analysis. RESULTS: Of the 58 (10 FAP and 48 UC) patients with complete data, 81% of UC and 80% of FAP patients reported dietary intolerances. Overall diet quality was good. Differences in dietary intake were limited to a few food groups. Patients with a history of pouchitis had a lower intake of fruits (p = 0.03) and nuts (p = 0.004). Patients with current pouchitis had a lower intake of nuts (p = 0.02). On multivariable logistic regression, intake of dietary fibre was associated negatively [OR 0.68(95%CI:0.51-0.92)] and of non-digestible oligosaccharides positively with pouchitis history [OR 5.5(95% CI:1.04-29.1)]. CONCLUSIONS: In patients with an ileoanal pouch, perceived dietary intolerances are common but had minimal impact on nutritional adequacy and diet quality. Negative associations of the intakes of fruits, nuts and dietary fibre and positive association with non-digestible oligosaccharides with a history of pouchitis require further study to inform dietary recommendations.

Detection of changes in regional colonic fermentation in response to supplementing a low FODMAP diet with dietary fibres by hydrogen concentrations, but not by luminal pH.

BACKGROUND: Carbohydrate fermentation plays a pivotal role in maintaining colonic health with excessive proximal and deficient distal fermentation being detrimental. AIMS: To utilise telemetric gas- and pH-sensing capsule technologies for defining patterns of regional fermentation following dietary manipulations, alongside conventional techniques of measuring fermentation. METHODS: In a double-blind crossover trial, 20 patients with irritable bowel syndrome were fed low FODMAP diets that included no extra fibre (total fibre content 24 g/day), or additional poorly fermented fibre, alone (33 g/day) or with fermentable fibre (45 g/day) for 2 weeks. Plasma and faecal biochemistry, luminal profiles defined by tandem gas- and pH-sensing capsules, and faecal microbiota were assessed. RESULTS: Plasma short-chain fatty acid (SCFA) concentrations (µmol/L) were median (IQR) 121 (100-222) with fibre combination compared with 66 (44-120) with poorly fermented fibre alone (p = 0.028) and 74 (55-125) control (p = 0.069), but no differences in faecal content were observed. Luminal hydrogen concentrations (%), but not pH, were higher in distal colon (mean 4.9 [95% CI: 2.2-7.5]) with fibre combination compared with 1.8 (0.8-2.8) with poorly fermented fibre alone (p = 0.003) and 1.9 (0.7-3.1) control (p = 0.003). Relative abundances of saccharolytic fermentative bacteria were generally higher in association with supplementation with the fibre combination. CONCLUSIONS: A modest increase in fermentable plus poorly fermented fibres had minor effects on faecal measures of fermentation, despite increases in plasma SCFA and abundance of fermentative bacteria, but the gas-sensing capsule, not pH-sensing capsule, detected the anticipated propagation of fermentation distally in the colon. The gas-sensing capsule technology provides unique insights into localisation of colonic fermentation. TRIAL REGISTRATION: ACTRN12619000691145.

Radiation exposure from radiological procedures in liver transplant candidates with hepatocellular carcinoma.

PURPOSE: Candidates for liver transplantation (LT) with hepatocellular carcinoma (HCC) undergo a large number of diagnostic and interventional radiology procedures. A significant proportion of such procedures involve ionizing radiation with increased lifetime risk of cancer. The objective of our study was to review LT candidates with HCC to quantify ionizing radiation doses from different radiology procedures performed at a single transplant center. METHOD: We retrospectively reviewed 179 adult patients with HCC (median age 58.6 years [IQR, 55-62]; 155 [86.6%] males) who were accepted for LT between April 2010 and Dec 2018. Radiology procedures and radiation doses were retrieved and the total and median radiation effective dose in millisieverts (mSv) were calculated for different procedures. Exposure to ionizing radiation was categorized based on previously reported thresholds. RESULTS: We assessed 9,986 radiology procedures for our cohort. Patients had a median effective dose prior to transplantation of 254 mSv (IQR, 130-421) with an annualized rate of 152 mSv (IQR, 92-266). Patient median dose increased to 316 mSv (IQR, 159-478) when including exposures post-LT within the study period. 85% of overall exposure was in the extremely high exposure category (>100 mSv). Interventional procedures represented 13% of procedures with substantial radiation and contributed to 45% of radiation exposure while abdominal CTs represented 39% of total procedures and contributed to 45% of radiation exposure. CONCLUSIONS: Patients with HCC considered for LT undergo radiology procedures with significant cumulative radiation exposure. Attempts to reduce radiation exposure are suggested by minimizing unnecessary procedures and utilizing ones without ionizing radiation. Improving interventional techniques to reduce radiation doses is needed without compromising treatment delivery.

Infliximab Trough Levels Are Associated With Transmural Sonographic Healing in Inflammatory Bowel Disease.

BACKGROUND: Mucosal healing improves clinical outcomes in patients with inflammatory bowel disease (IBD) and is associated with higher infliximab trough levels (ITLs). Transmural healing, assessed by intestinal ultrasound (IUS), is emerging as an objective target in Crohn's disease (CD) and ulcerative colitis (UC). This study explores the correlation between maintenance ITLs and sonographic transmural healing. METHODS: Patients on maintenance infliximab therapy were prospectively enrolled to undergo paired IUS examination and serum ITL. Infliximab trough levels were compared between patients with and without sonographic markers of inflammation using the Mann-Whitney U test. RESULTS: A prospective cohort of 103 patients (51% male; 79 CD; 24 UC; median duration of disease 8 years) underwent IUS and serum ITL testing. Forty-one percent of CD and 66% of UC patients demonstrated sonographic healing (bowel wall thickening ≤3 mm with no increase in color Doppler signal). Crohn's disease patients with sonographic healing had higher median ITL compared with those with sonographic inflammation (4.8 µg/mL vs 3.1 µg/mL; P = .049). Additionally, the presence of hyperemia on Doppler was independently associated with lower ITL compared with those without hyperemia (2.1 µg/mL vs 4.2 µg/mL, respectively; P = .003). There was no significant association between ITL and other sonographic markers of inflammation. In UC, lower ITL was associated with hyperemia on Doppler imaging (P = .04). There was no association between ITL and sonographic healing or any other individual sonographic parameter of inflammation. CONCLUSIONS: Lower maintenance infliximab levels are associated with sonographic parameters of inflammation in UC and CD. Further studies are needed to determine whether targeting higher infliximab levels can increase sonographic healing.

Transmural healing assessed by intestinal ultrasound allows for objective assessment of disease activity. Lower maintenance infliximab levels were associated with sonographic parameters of inflammation in IBD. Further studies are needed to determine whether targeting higher infliximab levels can increase sonographic healing.

A novel Monash Pouch diet in patients with an ileoanal pouch is tolerable and has favorable metabolic luminal effects.

Aims: To evaluate a whole-food diet strategy (the Monash Pouch diet [MPD]) designed based on the interacting roles dietary factors play with pouch health. Specifically, its tolerability and acceptability, whether it achieved its dietary and metabolic goals, and the effects on symptoms and inflammation were examined. Methods: In a 6-week open-label trial, patients with ileoanal pouches educated on the MPD were assessed regarding diet tolerability and acceptance, food intake (7-day food diaries), pouch-related symptoms (clinical pouchitis disease activity index), and, in 24-h fecal samples, calprotectin, fermentative biomarkers, and volatile organic compounds (VOC). Results: Of 12 patients, 6 male, mean (SD) age 55 (5) and pouch age 13 (2) years, one withdrew with partial small bowel obstruction. Tolerability was excellent in 9 (75%) and acceptance was high (81%). Targeted changes in dietary intake were achieved. Fecal branched- to short-chain fatty acid ratio increased by median 60 [IQR: 11-80]% (P = 0.02). Fecal VOCs for 3 compounds were also increased, 2-methyl-5-propan-2-ylcyclohexa-1,3-diene (Fold-change [FC] 2.08), 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane (FC 3.86), propan-2-ol (FC 2.10). All six symptomatic patients achieved symptomatic remission (P = 0.03). Fecal calprotectin at baseline was 292 [176-527] µg/g and at week 5 was 205 [148-310] µg/g (P = 0.72). Conclusion: Well tolerated and accepted, the MPD achieved targeted changes in intakes and fermentation of carbohydrates relative to that of protein. There were signals of improvement in symptoms. These results indicate the need for a randomized-controlled trial. (Trial registration: ACTRN12621000374864; https://www.anzctr.org.au/ACTRN12621000374864.aspx).

Value of computed tomography scores in complicated acute diverticulitis.

BACKGROUND: Diverticular disease remains one of the most common conditions in the western world. Up to 25% of patients with diverticular disease require hospitalization, 15-30% of those of which require surgical intervention. CT scoring systems have been proposed as means to drive assessment and stratify patients necessitating hospital intervention. To assess and correlate CT scoring systems with clinical and surgical outcomes. METHODS: Retrospective cohort analysis at a single institution. Single institutional assessment with patients presenting to emergency with a CT diagnosed episode of acute diverticulitis. One hundred and eighty-nine patients were included in the study, 61% of which were male. Patient demographics, comorbidities, medications, biochemistry and inflammatory markers, type of complication following acute diverticulitis, operative/procedural intervention, hospital outcome and mortality were measured. CT scoring systems assessed included modified Hinchey, modified Neff, World Society of Emergency Surgery (WSES) and modified Siewert scoring systems. RESULTS: Majority of patients had left-sided diverticulitis (91%) with localized air (88%) and pericolic abscess (49%) the most common radiological findings. 28% of patients required radiological and/or surgical management with 12% requiring intensive care unit (ICU) admission. There was a general trend for surgical/radiological intervention as the scores increased in severity. The four scoring systems were found to be statistically significant predictors of any intervention and of ICU admission with minimal statistical differences across the different scoring systems. CONCLUSION: Radiological CT scores for complicated diverticulitis are at best, moderate predictors of clinical and surgical outcomes and may serve to guide management with minimal statistical differences across different scores.

Portal Venous Pulsatility Index as a predictor of fibrosis in patients with non-alcoholic fatty liver disease.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a growing public health issue. Non-invasive methods to assess the fibrosis stage are limited, and biopsy remains the gold standard. The objective of our study was to assess whether the portal venous pulsatility index (VPI) can be used as a predictor of high-risk NAFLD at a tertiary referral centre for liver transplantation. METHODS: We retrospectively reviewed patients with biopsy-proved NAFLD who had undergone a liver ultrasound scan within 1 year of biopsy at our centre from 2011 to 2019. RESULTS: We did not find a significant correlation between the VPI and the NAFLD risk category or correlation between the VPI and degree of steatosis (P > 0.05 for both). CONCLUSION: Since VPI can be easily obtained on routine liver ultrasound and since other studies do report a positive association with significant fibrosis, more studies are needed before it can be recommended or not in risk-stratifying NAFLD patients into high- vs. low-risk NAFLD.

Toward transmural healing: Sonographic healing is associated with improved long-term outcomes in patients with Crohn's disease.

BACKGROUND AND AIMS: Transmural healing has emerged as a treatment target in Crohn's disease (CD). We investigated whether transmural healing assessed with intestinal ultrasound (IUS) is associated with improved clinical outcomes in patients with CD in clinical remission. METHODS: Patients with CD in clinical remission at baseline (HBI <4) having IUS between August 2017 and June 2020 with at least 6-months' follow-up were retrospectively studied. Time to medication escalation, corticosteroid use and CD-related hospitalisation or surgery were compared by the presence or absence of sonographic healing, defined as bowel wall thickness ≤3 mm without hyperemia on color Doppler, inflammatory fat, or disrupted bowel wall stratification. Factors associated with survival were analyzed by Kaplan-Meier analysis using Cox proportional-hazard model. RESULTS: Of 202 consecutive patients (50% male), sonographic inflammation was present in 61%. During median follow-up of 19 (IQR 13-27) months, medication escalation occurred in 52%, corticosteroid use in 23%, hospitalisation in 21%, and CD-related surgery in 13%. Sonographic healing was significantly associated with a reduced risk of medication escalation (p = 0.0018), corticosteroid use (p = 0.0247), hospitalisation (p = 0.0102), and surgery (p = 0.083). On multivariable analysis, sonographic healing was significantly associated with an increased odds of medication escalation-free survival (hazard ratio [HR]:1.94; 95% CI 1.23-3.06; p = 0.004) and corticosteroid-free survival (HR:2.41; 95% CI 1.24-4.67; p = 0.009), but not with hospitalisation or surgery. CONCLUSION: In patients with CD in clinical remission, sonographic healing is associated with improved clinical outcomes. Further studies are needed to determine whether sonographic healing should be a treatment target.

Accuracy of Gastrointestinal Ultrasound and Calprotectin in the Assessment of Inflammation and its Location in Patients with an Ileoanal Pouch.

BACKGROUND AND AIMS: In symptomatic patients with ileoanal pouches, pouchoscopy is needed for accurate diagnosis but is invasive. We aimed to assess the utility of non-invasive gastrointestinal ultrasound and faecal calprotectin in ileoanal pouch patients. METHODS: Patients with an ileoanal pouch were consecutively enrolled in this cross-sectional study from clinics in Victoria, Australia. The pouchitis disease activity index was used as a reference standard. Video-recorded pouchoscopies were reviewed by three gastroenterologists. Pouch, pre-pouch, and cuff biopsies were reviewed by a single pathologist. Ultrasound was performed by a single gastroenterologist transabdominally and transperineally. Faecal calprotectin was measured from morning stool samples. All examiners were blinded to patients' clinical history. RESULTS: A total of 44 participants had a pouchoscopy, of whom 43 had a faecal calprotectin test and 42 had an ultrasound; 17 had pouchitis, 15 had pre-pouch ileitis, and 16 had cuffitis. Pouch wall thickness of <3 mm was 88% sensitive in excluding pouchitis, and pouch wall thickness of ≥4 mm was 87% specific in diagnosing pouchitis. Transabdominal ultrasound had good utility [area under the curve: 0.78] in diagnosing moderate-severe pre-pouch ileitis. Transperineal ultrasound had good utility for the diagnosis of pouchitis [area under the curve: 0.79]. Faecal calprotectin differentiated inflammatory from non-inflammatory pouch disorders, such as irritable pouch syndrome, with an area under the curve of 0.90. Faecal calprotectin <100 µg/g ruled out inflammatory pouch disorders with a sensitivity of 94%. CONCLUSIONS: Faecal calprotectin and ultrasound are accurate and complementary tests to diagnose and localise inflammation of the ileoanal pouch. Prospective studies are needed to validate proposed sonographic indices and calprotectin levels.

The Reliability and Accuracy of Endoscopic Items and Scores Used in the Assessment of the Ileoanal Pouch and Cuff.

BACKGROUND AND AIMS: Currently used endoscopic items for the assessment of pouchitis and cuffitis have deficiencies in reliability and validation. We assessed the reliability and accuracy of new endoscopic items for pouchitis and of the Ulcerative Colitis Endoscopic Index of Severity [UCEIS] for cuffitis. METHODS: Three new endoscopic items were assessed and included in the Monash pouchitis endoscopic subscore: bleeding [absent/contact/spontaneous]; erosions [absent/<10/≥10]; and ulceration [absent/<10%/≥10%]. Three raters evaluated 44 pouchoscopy videos in duplicates, in random order. Intra- and inter-rater reliability of all endoscopic items and UCEIS were assessed. Clinical and histological pouchitis disease activity index [PDAI] subscores were also assessed and faecal calprotectin was measured. RESULTS: All three Monash endoscopic items had substantial intra-rater reliability with intraclass correlation coefficients [ICCs] >0.61 [95% CI >0.61], compared with only ulcers from the currently used PDAI endoscopic subscore, but inter-rater reliability was only substantial for ulceration and no better than those of the currently used endoscopic items. The Monash endoscopic subscore had a strong positive correlation with the reference standard global endoscopic lesion severity r = 0.80 [95% CI 0.80-0.80] and the reference standard PDAI endoscopic subscore r = 0.70 [95% CI 0.67-0.73], which was higher than the correlation observed for the currently used PDAI endoscopic subscore. The UCEIS had substantial intra-rater reliability, but only fair inter-rater reliability and poor diagnostic performance for cuffitis. CONCLUSIONS: The Monash endoscopic items, and endoscopic subscore they generate, have enhanced overall performance compared with the currently used PDAI items and subscore. Further validation and responsiveness to change in disease state are indicated.

Supplementing Dietary Fibers With a Low FODMAP Diet in Irritable Bowel Syndrome: A Randomized Controlled Crossover Trial.

BACKGROUND & AIMS: Institution of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) in patients with irritable bowel syndrome (IBS) may lead to inadequate fiber intake. This trial aimed to investigate the effects of supplementing specific fibers concomitantly with a low FODMAP diet on relevant clinical and physiological indices in symptomatic patients with IBS. METHODS: A double-blind crossover trial was conducted in which 26 patients with IBS were randomly assigned to 1 of 3 low FODMAP diets differing only in total fiber content: control, 23 g/d; sugarcane bagasse, 33 g/d; or fiber combination (sugarcane bagasse with resistant starch), 45 g/d. Each diet lasted 14 days with most food provided and ≥21 days' washout between. Endpoints were assessed during baseline and dietary interventions. RESULTS: From a median IBS Severity Scoring System total score at baseline of 305, all diets reduced median scores by >50 with no differences in rates of symptom response between the diets: control (57%), sugarcane bagasse (67%), fiber combination (48%) (P = .459). Stool output was ∼50% higher during the fiber-supplemented vs control diets (P < .001 for both). While there were no overall differences overall in stool characteristics, descriptors, and water content, or in gastrointestinal transit times, supplementation with sugarcane bagasse normalized both low stool water content and slow colonic transit from during the control diet. CONCLUSIONS: Concomitant supplementation of fibers during initiation of a low FODMAP diet did not alter symptomatic response in patients with IBS but augmented stool bulk and normalized low stool water content and slow transit. Resistant starch did not exert additional symptomatic benefits over sugarcane bagasse alone. (Australia and New Zealand Clinical Trial Registry; Number, ACTRN12619000691145).

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.