28April2022

Y-ECCO Literature Review: Lulia Al-Hillawi

Lulia Al-Hillawi

Accuracy of gastrointestinal ultrasound and calprotectin in the assessment of inflammation and its location in patients with an ileoanal pouch

Ardalan ZS, Friedman AB, Con D, et al.

JCC 2022;16:79–90


Lulia Al-Hillawi
© Lulia Al-Hillawi

Introduction

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is often the preferred surgical intervention for patients with medically refractory Ulcerative Colitis [1]. A significant proportion of patients with IPAA develop pouch-related symptoms characterised by increased pouch emptying, urgency, bloody exudates and cramps. Such symptoms can occur secondary to inflammatory disorders, including idiopathic pouchitis, which affects up to 50% of patients, or other conditions such as pre-pouch ileitis [2]. Symptoms can also be due to non-inflammatory disorders, with irritable-pouch dysfunction accounting for more than a third of symptomatic patients.

The most commonly accepted disease activity index is the Pouchitis Disease Activity Index (PDAI), which combines symptoms, endoscopy findings and histology. A total PDAI 7 is considered diagnostic for pouchitis but is not specific [3].

The gold standard investigation is pouchoscopy, which allows endoscopic and histological assessment of the pouch, pre-pouch ileum and cuff [4]. However, it is an invasive and often uncomfortable procedure for patients. In some cases the alternative strategy of empirical antibiotic therapy for every symptomatic episode is adopted, but this comes with the risks associated with unnecessary antibiotic use.

In this cross-sectional study, Ardalan et al. sought to assess the role of non-invasive gastrointestinal ultrasound (GIUS) and faecal calprotectin (FCP) testing in the investigation of pouchitis.

Methods

Consecutive patients were recruited from Inflammatory Bowel Disease (IBD)/surgical clinics in Victoria, Australia over a 2-year period. Data on clinical history and pouch function were gathered at a baseline visit, and stool was collected for FCP testing. GIUS was performed by a single gastroenterologist with >8 years’ experience who was blinded to the history and endoscopic findings. Both transabdominal and transperineal ultrasound was performed. Six recognised GIUS parameters for IBD were assessed: bowel (pouch) wall thickness, presence/absence of hyperaemia using colour Doppler signal, preservation of wall stratification, degree of peristalsis, presence/absence of mesenteric hyperechogenicity and presence/absence of lymphadenopathy [5].

Patients then underwent a pouchoscopy and biopsies. Video recordings of the pouchoscopies were blindly scored by three gastroenterologists with >10 years’ experience who had undergone pre-study online training and participated in a study meeting. The histological subscore was completed by a single experienced pathologist who was blinded to clinical history.

Key Findings

A total of 44 patients underwent pouchoscopy, of whom 43 had FCP testing and 42 had GIUS. All patients had a J pouch, with a mean pouch age of 13.5 years. The majority were male (63%), with mean age of 50 years. Seventeen had pouchitis, 15 had pre-pouch ileitis and 16 had cuffitis. Clinical PDAI subscores did not correlate with endoscopic/histological subscores.

FCP was significantly higher in patients with any inflammatory pouch condition. FCP <100 µg/g ruled out any pouch inflammatory condition (sensitivity 89%, negative predictive value 79%). However, FCP was not significantly different between those with pouchitis with or without pre-pouch ileitis and those with isolated pre-pouch ileitis. FCP ³350 µg/g was useful in the diagnosis of pouchitis with endoscopic and acute histological evidence of inflammation (specificity 83%, positive predictive value 83%). FCP demonstrated a strong positive correlation with total PDAI and PDAI endoscopic and histological subscores.

The transabdominal ultrasound assessment gave good views of the pre-pouch ileum in 97% of patients, and pre-pouch ileitis could be confidently diagnosed using bowel wall thickness, presence of hyperaemia and presence of lymphadenopathy, with moderate discriminative performance.

To accurately assess the pouch, a transperineal approach was needed (adequate views were obtained in 78% of cases when using a convex probe and in 85% when using a microconvex probe). However, only pouch wall thickness showed a significant difference between the pouchitis group and the non-pouchitis group. A pouch wall thickness ≥4 mm was found in this study to be equivalent to a PDAI endoscopic and histological score of ≥4, with a specificity of 100%. Wall thickness showed a strong positive correlation with the severity of pouchitis in this cohort.

Whilst 97% of cuff views were considered good quality when using the transperineal approach, none of the ultrasound features showed significant differences between the cuffitis and the non-cuffitis group.

Discussion

Non-invasive biomarkers such as FCP have an established role in the assessment of IBD, with benefits including cost and patient preference, and FCP has been shown to be relevant in pouchitis [6,7].

Ardalan et al. have shown that while FCP can also be a helpful tool in distinguishing between inflammatory and non-inflammatory pouch conditions, it does not determine the severity or location of inflammation. The useful ‘cut-offs’ of <100 µg/g for non-inflammatory conditions and ³350 µg/g for pouchitis can be adopted sensibly in clinical practice to reduce the need for repeated invasive pouchoscopy in those with previously proven idiopathic pouchitis.

GIUS is yet to be validated in the assessment of pouchitis [8]. Whilst this study demonstrated the ability of GIUS to assess pouch wall thickness in pouchitis, and was able to identify pre-pouch ileitis, there were several limitations: the patient cohort was relatively small, GIUS was performed by a single expert gastroenterologist, precluding assessment of inter-reader reliability, and no data were provided regarding the learning curve for ultrasound techniques in the assessment of pre-pouch ileum and pouch. Furthermore, longitudinal assessment was not performed. Aside from the issue of validation of GIUS in pouchitis, ultrasound training for gastroenterologists is not commonplace in certain areas, and the cost of training and equipment should be considered [9].

Further prospective multicentre studies are required to validate the role of GIUS in diagnosing pouchitis. The use of FCP in those with recurrent pouchitis may allow the avoidance of repeated pouchoscopy.

References

  1. Fazio VW, Kiran RP, Remzi FH, et al. Ileal pouch anal anastomosis: analysis of outcome and quality of life in 3707 patients. Ann Surg. 2013;257:679–85.
  2. Akiyama S, Rai V, Rubin DT. Pouchitis in inflammatory bowel disease: a review of diagnosis, prognosis, and treatment. Intest Res. 2021;19:1–11.
  3. Sandborn WJ, Tremaine WJ, Batts KP, Pemberton JH, Phillips SF. Pouchitis after ileal pouch-anal anastomosis: a Pouchitis Disease Activity Index. Mayo Clin Proc. 1994;69:409–15.
  4. Samaan MA, Shen B, Mosli MH, et al. Reliability among central readers in the evaluation of endoscopic disease activity in pouchitis. Gastrointest Endosc .2018;88:360–9.
  5. Furfaro F, Dal Buono A, Allocca M, et al. Bowel ultrasound in inflammatory bowel disease: how far in the grayscale? Life (Basel). 2021;11:649.
  6. Walsham NE, Sherwood RA. Fecal calprotectin in inflammatory bowel disease. Clin Exp Gastroenterol. 2016;9:21–9.
  7. Johnson MW, Maestranzi S, Duffy AM, et al. Faecal calprotectin: a noninvasive diagnostic tool and marker of severity in pouchitis. Eur J Gastroenterol Hepatol. 2008;20:174–9.
  8. Maaser C, Sturm A, Vavricka SR, et al. European Crohn’s and Colitis Organisation [ECCO] and the European Society of Gastrointestinal and Abdominal Radiology [ESGAR]. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD. Part 1: Initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis. 2019;13:144–64
  9. Bryant RV, Friedman AB, Wright EK, et al. Gastrointestinal ultrasound in inflammatory bowel disease: an underused resource with potential paradigm-changing application. Gut. 2018;67:973–85.

Lulia Al-Hillawi - Short Biography

Lulia Al-Hillawi is currently working as a Clinical Research Fellow in IBD at the Translational Gastroenterology Unit at the John Radcliffe Hospital in Oxford, with a particular interest in immunotherapy-related GI toxicities.

Posted in ECCO News, Y-ECCO Literature Reviews, Committee News, Volume 17, Issue 1, Y-ECCO