Knowledge and perspectives towards the use of histology in inflammatory bowel disease by gastroenterologists across the Asia-Pacific region
Article information
Abstract
Background/Aims
Recently, histological mucosal assessment has gained momentum as a potential new treatment target for patients with inflammatory bowel disease (IBD) in the Asia-Pacific region. This study aimed to evaluate and compare the knowledge and acceptability of histological assessment among gastroenterologists across the region.
Methods
A cross-sectional survey among gastroenterologists in the Asia-Pacific region was conducted and compared against a previous Australian survey. The questionnaire assessed knowledge and attitude towards the role and application of histology in IBD practice. Statistical analyses were employed to compare scores and identify predictors.
Results
A total of 221 gastroenterologists from 12 countries, including 77 (34.8%) from Australia, responded to questionnaire, with 185 (83.7%) completing the survey. The mean knowledge score was 9.8 ± 3.3 (51.6%). There was no significant difference in the average score among countries (P= 0.53). IBD specialist (P< 0.01), doctoral degree (P= 0.02), and regular participation in IBD multidisciplinary meetings (P= 0.01) were associated with higher scores. Most respondents (90.7%) agreed on the importance of histology in IBD. While 54.6% of Australians perceived the role of histology as established, only 37.0% of Asians respondents considered this similarly (P= 0.02). Histological activity alone minimally influences treatment escalation in patients with endoscopic remission, but achieving combined histo-endoscopic remission often leads to therapy de-escalation.
Conclusions
Although gastroenterologists in the Asia-Pacific region are aware of the role of histology in IBD, their knowledge remains limited, and its clinical utility is not widely adopted. There is a need to promote the routine use of standardized histological assessment in IBD practice.
INTRODUCTION
Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn’s disease, presents a significant healthcare challenge globally, with its prevalence steadily rising, particularly in the Asia-Pacific region [1-3]. This chronic inflammatory condition manifests with relapsing episodes, often leading to debilitating outcomes such as hospitalization, surgical interventions, and diminished quality of life [4]. The conventional approach to managing IBD has focused on achieving clinical and endoscopic remission, as advocated by the Selecting Therapeutic Targets in Inflammatory Bowel Disease-II consensus [5]. However, emerging evidence suggests that histological assessment and outcome may also play a pivotal role in understanding disease activity and predicting long-term outcomes of IBD patients [6-8].
While histological remission has been recognized in most contemporary clinical drug trials, its formal integration as a treatment target in routine practice remains unexplored. Despite recent surveys indicating a high level of awareness regarding the significant role of histology in IBD [9], there remains a substantial gap in both knowledge and utilization of histopathology among gastroenterologists and pathologists. This underscores the critical need to enhance education among clinicians, which may help on conducting further research in this topic and ensuring greater familiarity in clinical practice.
Given lower IBD prevalence, it is not known whether gastroenterologists in Asia-Pacific region are aware of or utilize histopathological assessment. Variability in practice standards among Asian countries might also include the availability of gastroenterologists to interpret biopsy results. In this context, we expanded our survey to evaluate the knowledge of histological assessment in IBD among healthcare professionals in the Asia-Pacific region. Additionally, we sought to assess their attitudes towards the role of histology in IBD assessment and management, with a particular focus on comparing Australian and Asian practices. We hypothesized that Australian healthcare professionals may have more extensive knowledge and experience with histological assessment in IBD compared to Asian gastroenterologists due to a greater volume of IBD-focused work. While knowledge about histological assessment in IBD may be increasing in Asian countries, its integration into routine clinical practice may still be limited due to resource limitations. Comparing attitudes and practices among these countries will help identify disparities and promote the harmonization of histological approach to enhance patient care standards across the Asia-Pacific region.
METHODS
We conducted a prospective, cross-sectional survey of gastroenterologists in the Asia-Pacific region from May to September 2023. This survey was administered online, disseminated through members of the Asian Pacific Association of Gastroenterology and their affiliated local societies. The data obtained from this survey were amalgamated with that from a prospective, cross-sectional survey of Australian gastroenterologists conducted earlier in 2022 [9]. In the Australian survey, healthcare professionals were contacted by proxy through the Gastroenterological Society of Australia to participate. The questionnaire used in both surveys contained identical questions. Participation in the survey was voluntary, and consent was implied by the completion of the survey. No personally identifiable data were collected from the participants, and there were no questions linking patients. The study was approved by the Sydney Local Health District Human Research Ethics Committee (HREC 2021/PID00882).
1. Survey on Attitudes and Knowledge towards Histology in IBD
The structured survey was developed by a team of gastroenterologists, drawing from the European Crohn’s and Colitis Organisation (ECCO) position paper on histopathology [10,11], and biopsy reporting guidelines of the British Society of Gastroenterology [12]. The survey encompassed demographic details and practice locations of respondents. Attitudes towards the histology and its application in clinical practice were asked through 8 questions (Supplementary Material). Additionally, the survey comprised 18 questions assessing histological knowledge, covering important topics such as commonly used histological scoring systems, including Truelove and Richards Index [13], Modified Riley score [14], Geboes score [15], Nancy histological index (NHI) [16], Robarts histopathology index (RHI) [17], and the potential role of histological assessment in managing IBD. This questionnaire was discriminately validated by comparing responses from senior and junior gastroenterologists practicing in Australia who were not involved with the questionnaire development. A knowledge score was derived by summing correct responses, with a maximum possible score of 19.
2. Statistical Analysis
Continuous variables were depicted as mean ± standard deviation, while categorical variables were represented by the number of subjects and corresponding percentages. To compare the knowledge of IBD histology across different factors, a standard independent t-test and chi-square test were employed. One-way analysis of variance was used to compare the means of more than 2 continuous variables. Predictors of IBD histology knowledge scores were determined through linear regression analysis. A significance level of < 0.05, two-tailed, was deemed statistically significant. All statistical analyses were conducted using STATA 17.0 (Stata Corporation, College Station, TX, USA).
RESULTS
The study involved a total of 221 gastroenterologists from 12 countries across the Asia-Pacific region. The 3 countries with the highest number of respondents were Australia (n = 77, 34.8%), Taiwan (n = 41, 18.6%), and Singapore (n = 32, 14.5%). Detailed demographic information is shown in Table 1. Out of the total, 185 respondents (83.7%) completed the survey, with a mean completion time of 9.39 minutes. The majority of respondents fell within the 31 to 40 years age group and held either Doctor of Medicine (MD), Bachelor of Medicine, Bachelor of Surgery (MBBS), or a gastroenterologist fellowship degree. Approximately one-third were general gastroenterologists, another one-third specialized in IBD, and 15.8% were in training. Most of the respondents worked in public hospitals and reported seeing at least 5 IBD patients each week in their respective hospitals. Nearly half (48%) reported regular participation in IBD multidisciplinary team (MDT) meetings, occurring at least once a month in their IBD unit. Besides the respondents, surgeons were the most frequent participants in the MDT meetings, followed by radiologists and pathologists, respectively. No differences were observed in demographic data between Australian and non-Australian respondents.
Demographic Data
1. Knowledge of Histology in IBD across the Asia-Pacific Region
The mean IBD histological knowledge score among 185 respondents was 9.8 ± 3.3 out of 19 (51.6%). The mean scores of the majority of respondents, including those from Australia, Singapore, Taiwan, and Thailand, were 9.2 ± 3.2, 10.8 ± 3.6, 10.5 ± 4.0, and 9.6 ± 1.8, respectively (Fig. 1). While the difference in mean scores among each country was not statistically significant (P= 0.53), there was a trend toward higher knowledge scores in Asian countries compared to Australia (P= 0.06). Gastroenterologists specialized in IBD had significantly higher knowledge scores compared to non-IBD gastroenterologists (P< 0.01; mean difference, –2.26; 95% confidence interval [CI], –3.25 to –1.27) (Fig. 2). Gastroenterologists holding a Doctor of Philosophy (PhD) degree exhibited higher knowledge scores relative to those with lower degrees (P= 0.02; mean difference, –1.34; 95% CI, –2.47 to –1.99). Gastroenterologists who regularly participated in IBD-focused MDT meetings had higher knowledge scores compared to those who did not have meetings in their hospitals (P= 0.01; mean difference, –1.27; 95% CI, –2.22 to –0.32). There were no significant differences in knowledge scores between gastroenterologists working in public or university hospitals compared to those in private hospitals (P= 0.16; mean difference, –0.99; 95% CI, –2.38 to 0.38). Similarly, no significant differences were observed between practicing gastroenterologists and those still in training (P= 0.28; mean difference, –0.70; 95% CI, –2.02 to 0.61). Data for Asian and Australian respondents are presented separately in Supplementary Fig. 1. Among the validated histological scoring systems, including the NHI and RHI scores, only 42 respondents (22.7%) were aware of the NHI remission cutoff of 0, and only 28 respondents (15.1%) were aware of the RHI cutoff level of ≤ 3 to identify histological remission. Fig. 3 shows the comparison of histological remission knowledge for each scoring system. IBD specialists are more aware of both remission endpoints than those who are not specialized in IBD (P< 0.01).
Mean inflammatory bowel disease (IBD) histological knowledge scores of overall respondents and the 4 most responsive countries. Values are shown in mean±standard deviation.
Forest plot comparing inflammatory bowel disease (IBD) histological knowledge of all respondents according to IBD subspecialty, educational degree, primary workplace, level of training, and participation in multidisciplinary team meeting. Values are shown in mean±standard deviation and mean difference with 95% confidence interval. PhD, Doctor of Philosophy; MDT, multidisciplinary team.
Comparison of knowledge of histological remission endpoint for each scoring system. (A-C) The remission endpoints of Geboes score, Nancy histological index, and Robart’s histological index are ≤2, 0, and ≤3, respectively.
We identified several predictive factors associated with adequate histological knowledge, using a knowledge score of greater than 10 as the threshold. Among all respondents, being an IBD specialist was strongly associated with higher knowledge scores in both univariable (odds ratio [OR], 3.55; 95% CI, 1.86 to 6.75; P< 0.01) and multivariable analyses (OR, 2.66; 95% CI, 1.30 to 5.45; P= 0.01). Holding a PhD degree and regular MDT participation also showed significance in univariable analysis (OR, 2.81; 95% CI, 1.40 to 5.68; P< 0.01 and OR, 2.14; 95% CI, 1.18 to 3.89; P= 0.01, respectively) but not in multivariable analysis. The results of univariate and multivariate analyses for each subgroup are demonstrated in Table 2.
Predictive Factors for Histological Knowledge
2. Attitudes towards Histology and Scoring Systems in IBD
Overall, respondents widely agreed on the significance of histology in IBD, with a majority describing this as “emerging” (47.3%) or “established” (43.4%). Notably, while 54.6% of Australian gastroenterologists perceived the role of histology as established, only 37.0% of respondents from Asia considered similarly (P= 0.02) (Fig. 4A). Similarly, Australian gastroenterologists supported the idea that achieving histological remission is more crucial than endoscopic remission, with 65.0% agreement, while only 18.5% of Asian respondents agreed on this statement. The respondents reported that 65.4% of the official IBD pathological reports do not incorporate histological scoring systems. Among the standard scores, the NHI was the most widely utilized (75.0%), followed by the Geboes score (10.9%). A significant proportion of Australian respondents (28.6% always and 29.9% sometimes) showed a preference for utilizing scoring systems. Conversely, Asian respondents have not yet preferred, with 33.3% indicating never and 27.8% rarely (Fig. 4B).
Attitudes of gastroenterologists in the Asia-Pacific region towards the role of histology in clinical practice (A) and the current preference of using histological index in routine practice (B).
3. Impact of Histological Information on Clinical Practice
The extent of histological activity in influencing IBD management was explored (Supplementary Table 1). Most gastroenterologists indicated that histological activity would not prompt a change in treatment if patients were already in endoscopic remission. However, when combined with elevated fecal calprotectin, escalation of therapy was occasionally initiated. In cases where patients achieved combined histo-endoscopic remission during 2 consecutive colonoscopies, most gastroenterologists would consider treatment de-escalation (44.6% responded “often” and 12.7% reported “always”). Conversely, if a prior colonoscopy showed a Mayo endoscopic score (MES) of 1, fewer respondents would de-escalate treatment. An MES of 1 was insufficient for most gastroenterologists to de-escalate treatment. Given that histological activity might be linked to dysplasia, 67% of gastroenterologists would aim for histological remission in UC patients with additional risk factors for colorectal cancer.
DISCUSSION
Despite histological remission not yet being a formal treatment target in IBD, the concept of disease clearance has evolved to incorporate histological remission as an endpoint due to its association with a lower risk of hospitalization and disease relapse [18]. With this emerging knowledge, our team conducted a survey on gastroenterologists across the Asia-Pacific region to assess knowledge and attitudes towards the role of histology in IBD, aiming to understand the level of knowledge and their perspectives on histological assessment as a potential new treatment target. The survey found that the majority of gastroenterologists exhibited limited histological knowledge, scoring a mean of only 51.6%, with slightly higher scores in Asian respondents. Australian gastroenterologists demonstrated more supportive stance towards the role of histology in IBD practice, with substantial acceptance of histological remission as an ultimate goal of IBD treatment. Conversely, in Asia, while there was acknowledgment of this importance, the integration into clinical practice remained in the nascent stage.
A knowledge questionnaire based on the ECCO histopathology statement highlighted common IBD histological findings and treatment targets, including neutrophilic inflammation for defining histological activity, and absence of neutrophils, erosion, or ulceration for histological remission. Histological non-remission may predict complications and increase the risk of colonic neoplasia [19,20]. The NHI cutoff level of 0 and RHI of ≤ 3, which signify either the absence or mild increase of chronic inflammatory infiltrates, are recognized to determine histological remission [10,21]. Interestingly, respondents demonstrated insufficient knowledge of histological findings, as well as unawareness of cutoff levels for histological remission. Self-reporting as an IBD specialist is the predictive factor for better knowledge, implying that knowledge of this area is confined to a specific subgroup of gastroenterologists. While evidence supporting the benefits of histological remission is increasing, our survey found limited utilization of histology among respondents, who continue to prioritize biochemical and endoscopic outcomes. This highlights the urgent need to improve the histological knowledge in the Asia-Pacific region, especially among general gastroenterologists, to ensure standardized management and improved patient care.
Danese and his colleagues recently conducted a global survey on 359 participants from 60 countries on the real-world use of histological indices in UC [22]. Nearly all respondents (90.5%) use UC histology primarily for initial diagnosis whereas a smaller percentage use it to monitor or confirm disease remission. Our study, where all responses were from the AsiaPacific region, aligns with the global survey, indicating that up to 90% of respondents recognized the importance of the histological role in IBD. The disparities in IBD practice between Asia and Australia potentially led to differing attitudes in their histological applications. In Australia, where IBD has been acknowledged and extensively studied, along with abundant access to resources, including various non-gastroenterologist involvement in the unit, foster higher acceptance of histological assessments. Conversely, IBD practice in Asia has only gained prominence over the past decade [2,23]. Additionally, the historical emphasis on endoscopic technology in this region may limit the use of histology at present. The complexity of scoring systems and the absence of large prospective studies confirming the impact of histological activity on clinical outcomes of IBD patients are also significant factors contributing to the limited use of histological indices. It is important to note that although histology has become increasingly important, uncertainty remains regarding the optimal number and site of biopsies, as well as the ideal timing for assessment. The heterogeneity in practice across different countries also affect the interpretation of histological findings. Additionally, histological assessment in Crohn’s disease can be challenging due to the limited use of the histological index and the difficulty in accessing affected segments. Due to the current lack of robust data, histological endpoint cannot yet be considered a standard treatment outcome.
Our study is the first survey conducted on this topic in the Asia-Pacific region, carried out on behalf of large international gastroenterological organizations. It provides comprehensive data and comparative analysis of both Asian and Australian gastroenterologists, where the prevalence of IBD and establishment of practice differ significantly. This survey also covered multiple aspects, including the assessment of histological knowledge and the attitudes towards using histology in routine practice. However, there are some limitations. Firstly, the coverage of our survey was incomplete, as we did not receive responses from every country in the region, and the proportion of respondents from each country was disproportionate. Secondly, as an online survey, not all participants answered every question, which possibly due to the length of survey and language barriers. Nonetheless, the robust findings were supported by a substantial number of participants and consistent trends. Lastly, there was a temporal discrepancy between the Australian and Asian surveys which may have introduced nuances in histological knowledge.
In conclusion, while most gastroenterologists in the Asia-Pacific region are aware of the role of histology in IBD, they possess limited knowledge and do not routinely apply it in clinical practice. Enhancing histological knowledge and promoting the use of histological evaluations, possibly through implementing standardized reporting and artificial intelligence, conducting more histological studies, and building a consensus agreement in the region, will help gastroenterologists gain better comprehension and become more familiar with using standardized histological assessments.
Notes
Funding Source
The authors received no financial support for the research, authorship, and/or publication of this article.
Conflict of Interest
Leong RW is an editorial board member of the journal but was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.
Data Availability Statement
Data, analytic methods, and study materials are available to other researchers upon request.
Author Contributions
Conceptualization: Leong RW. Formal analysis: Chaemsupaphan T, Lin H. Investigation: Chaemsupaphan T, Pudipeddi A, Lin H, Wu HY, Limsrivilai J, Lim WC, Wei SC. Methodology: Chaemsupaphan T, Pudipeddi A, Lin H, Leong RW. Supervision: Leong RW. Writing - original draft: Chaemsupaphan T, Leong RW. Writing - review & editing: Pudipeddi A, Leong RW. Approval of final manuscript: all authors.
Additional Contributions
We would like to extend our gratitude to the Asian Pacific Association of Gastroenterology (APAGE) Steering Committee for Histology in Inflammatory Bowel Disease for their invaluable assistance in disseminating our survey.
Supplementary Material
Supplementary materials are available at the Intestinal Research website (https://www.irjournal.org).
Supplementary Material.
Inflammatory bowel disease histology survey questions
Supplementary Table 1.
Impact of Histological Information towards Clinical Practice
Supplementary Fig. 1.
Comparison of inflammatory bowel disease (IBD) histological knowledge among Asian (A) and Australian (B) respondents according to IBD subspecialty, educational degree, primary workplace, level of training, and participation in multidisciplinary team meeting. PhD, Doctor of Philosophy; MDT, multidisciplinary team.