Introduction

The risk of synchronous colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) and high-grade dysplasia (HGD) is not known.

Aims & Methods

Study aim was to compare the risk of colorectal cancer at index colonoscopy in patients with HGD and IBD to patients with HGD without IBD. We also sought to evaluate the current management of visible HGD and invisible HGD, identified on random biopsies, in IBD. A retrospective cohort study was conducted. Through pathology database search, we identified all 1283 consecutive patients with an endoscopically resected colorectal HGD (biopsy or polypectomy), between 2010 and 2019 at the University of Montreal Hospital Center. We included patients aged 45-75 and excluded patients with polyposis syndromes, a history of CRC or index sigmoidoscopy. Files were reviewed for demographic data, index findings, IBD characteristics, and HGD management. Primary outcome was the risk of synchronous CRC at index colonoscopy in patients with HGD and IBD versus HGD and no IBD. Synchronous CRC was defined as CRC on index or CRC identified on surgery as the underlying lesion from which HGD was biopsied. Secondary outcomes were the proportion of visible and invisible HGD in IBD managed surgically. Continuous and categorical variables were compared using the Student t test, Pearson’s chi-squared test, or Mann-Whitney test. Multivariable logistic regression analysis was performed for the primary outcome.

Results

Overall, 982 patients with HGD without IBD (mean age 63 years; 55% male), and 37 patients with HGD and with IBD (mean age 59 years; 78% male; 62% ulcerative colitis; 38% Crohn’s disease; median time from IBD diagnosis to HGD is 17.0 years, mean 19.9 ± 13.4 years) were eligible based on inclusion and exclusion criteria above. In the HGD without IBD group, 294 patients out of 982 (29.9%) had synchronous CRC, with 260 CRCs found in the lesion where HGD was biopsied (26.5%), and 34 CRCs found in another location (3.5%). In the HGD with IBD group, 18 patients out of 37 (48.6%) had synchronous CRC, with 16 CRCs found in the lesion where HGD was biopsied (43.2%), and 2 CRCs found in another location (5.4%). Patients with HGD and IBD were more likely to have synchronous CRC compared to HGD and no IBD (odds ratio 2.22, 95%CI: 1.15-4.29). Out of 37 patients with IBD and HGD, 26 were managed surgically (70.3%), with 17 undergoing total colectomies, 4 right hemicolectomies, 4 transanal excisions, and 1 low anterior resection. Out of 37 patients with IBD and HGD, 8 had invisible HGD (21.6%) and all underwent total colectomy.

Conclusion

Patients with HGD and IBD are significantly more likely to have synchronous CRC compared to patients with HGD without IBD, with half of patients with HGD and IBD having synchronous CRC. Most patients with IBD and HGD are managed surgically, usually by total colectomy.

Disclosure

None

Introduction

Eosinophilic oesophagitis (EoE) is a chronic, progressive, immune-mediated disease of the esophagus. Solid food dysphagia combined with eosinophil (eos)-dominant inflammation (≥ 15 eos/high-power-field (HPF)) serve as diagnostic criteria. Treatment goals in active EoE are induction of (RI) and maintenance of remission (RM). Topical budesonide therapy in form of an orodispersible tablet (BUD-ODT) proved to be effective in both.

Aims & Methods

This retrospective study from two German EoE centers examined the efficacy and safety of BUD-ODT therapy in adults with active EoE over a period of four years (6/2018 - 8/2022) using clinical (Straumann Dysphagia Score, DSQ) and histological (eos/HPF) evaluations. Clinico-histological remission was defined as a DSQ of 0-3 (max. 9) and ≤ 15 eos/HPF. The results of three periods were evaluated: Induction phase (RI: 2x1 mg daily, 6-12 weeks (wks); n=212), maintenance phase 1 (RM1:1x1mg, 2x0.5mg or 1x0.5 mg daily, 14-24 wks; n=114), and maintenance phase 2 (RM2: same dosage as in RM1, 52-104 wks; n=77).

Results

232 patients (pts) were initially included: 69.0% male; mean age: 43.2 years (y) (median: 41 y, range: 17-83 y); median time to first diagnosis of EoE: 2.5 y (range: -7 y).
After 6-12 wks of induction therapy, 76.4% (162/212) of pts were in clinico-histological remission. After 14-24 wks (RM1), 74.6% (85/114) of pts presented in clinico-historical remission. At this point, recurrence rate was 21.9% (25/114): 68.0% (17/25) had a histological, 16.0% (4/25) a clinical (in the case of strictures) and 16.0% (4/25) a clinico-histological relapse during 14-24 wks of maintenance therapy. Finally, after 52-104 wks of BUD-ODT therapy (RM2), 77.9% (60/77) of pts presented with a clinico-histological remission. The overall relapse rate after 52-104 wks was 16.9% (13/77): 46.2% (6/13), experienced histological, 53.8% (7/13) clinical and 7.7% (1/13) clinico-histological)) recurrence. All 38 pts with a relapse either after 14-24 wks or 52-104 wks received a reinduction therapy (Table 1). Of those, 42.1% (16/38) pts again achieved a clinico-histological remission at the last follow-up visit.
Pts with an EoE relapse underwent:

No clinico-histological remission:	Further treatment		Percentage (%) and number (n) of patients
After RI, Weeks 6-12 (23.6%, 50/212)	Prolongation of RI		52.0% (26/50) 57.7% (15/26) in clinico-histological remission at follow-up
	Discontinuation of therapy, study exclusion*		30.0% (15/50)
	Maintenance therapy due to clinical well-being*		18.0% (9/50)
Weeks 14-24 (RM) (25.4%, 29/114)	Reinduction therapy (Re-IT) due to relapse		86.2% (25/29) 36.0% (9/25) in clinico-histological remission at follow-up
	Discontinuation of therapy*		13.8% (4/29)
Weeks 52-104 (22.1%, 17/77)	Reinduction therapy (Re-IT) due to relapse		76.5% (13/17) 46.2% (6/13) in clinico-histological remission at follow-up
	Unclear procedure		23.5% (4/17)
Therapy discontinuation	Overall		11.6% (27/232)
	Reasons:	Adverse events: 6.5% (15/232) Noncompliance: 5.2% (12/232)

Table 1: Treatment after failing induction of remission or recurrence under maintenance treatment, *poss. Re-IT or discontinuation of therapy
The most common side effect was endoscopically detected combined oral-esophageal candidiasis (17.9% (38/212) of pts after 6-12 wks, 7.9% (9/114) after 14-24 wks and 15.6% (12/77) after 52-104 wks), which was successfully treated with an oral antifungal agent.

Conclusion

With a remission induction rate of 76.4% and a maintenance of remission of 74.6% after RM1 and 77.9% after RM2 the BUD-ODT presented as effective and safe in a real-world setting in adults with active EoE. Similar results (77.7% of pts with BUD.ODT 2x0.5mg in remission after 48 wks and 82.5% after 96 wks) are published in randomized, placebo-controlled studies (Straumann A. et al, Gastroenterology 2020;159:1672–1685). The spectrum of side effects did not show any new aspects.

References

Straumann A. et al, Gastroenterology 2020;159:1672–1685

Introduction

The distinction between eosinophilic esophagitis (EoE) and other causes of dysphagia in clinical practice can be difficult without histology. In addition, failure to collect esophageal biopsies represents one of the reasons for a delayed diagnosis in patients with EoE. Current guidelines recommend multiple esophageal biopsies in all patients reporting dysphagia although this may not be cost-effective.

Aims & Methods

To optimize resources allocation in the diagnostic workup of EoE, we developed and thereafter validated on an independent cohort of patients two point-of-care machine learning (ML) tools to predict a diagnosis of EoE: 1) based on clinical history data alone and 2) based on clinical-endoscopic findings, prior to the results of esophageal biopsies. This was a two-step multi-center international study conducted in three European tertiary referral centers for EoE (London, Pisa, and Padua). We build predictive ML models based on retrospectively extracted clinical data alone (age at diagnosis, sex, presence or absence of heartburn, chest pain, postprandial nausea/dyspepsia, history of food impaction requiring endoscopic removal, allergic rhinitis, asthma, nasal polyposis) and on clinical and upper endoscopy (EGDS) (exudates, rings, edema, furrows, stricture) data collected from 273 EoE and 55 non-EoE dysphagia (NED) patients in London. We performed an external validation of the models on an independent cohort of 93 prospectively enrolled patients reporting dysphagia at Pisa and Padua University Hospitals. The performance of the models was described with area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). We then developed a freely downloadable software for use in clinical practice at the point-of-care.

Results

The machine learning model trained on clinical data alone showed AUC of 0.82, and sensitivity, specificity, PPV, and NPV of 0.75, 0.82, 0.82, 0.75, respectively, for the diagnosis of EoE in the external validation cohort. Among clinical data alone, the patients’ age at diagnosis and sex had the highest predictive ability. The machine learning model trained on a combination of clinical and endoscopic data showed AUC of 0.93, and sensitivity, specificity, PPV, and NPV of 0.88, 0.95, 0.95, 0.87, respectively, in the external validation cohort. Among clinical and endoscopic data, the patients’ age at diagnosis, esophageal rings at endoscopy, and sex had the highest predictive ability. The models’ performance in the development and external validation cohorts is reported in Table 1.

Conclusion

The international external validation of our ML tools, as well as the freely available software, allow generalizability of our findings to other settings. Our software can be easily used at the point-of-care to optimize resources allocation in the diagnostic workup of EoE and 1) Support the clinical suspicion of EoE even in the absence of endoscopic findings, 2) Support decision making in performing repeat EGDS in patients in whom biopsies had been omitted, 3) Support decision making in performing repeat EGDS in patients with persistent EoE symptoms who had non-diagnostic levels of eosinophils at a previous EGDS performed while on proton-pump inhibitors, 4) Avoid unnecessary biopsies in very low-risk patients.

Introduction

Treatment of rectal cancer requires an understanding of presenting stage and therapeutic modalities to provide appropriate and effective multimodality approaches that are oncological sound and respectful in terms of organ preservation and survivors’ quality of life. Imaging (endoscopic ultrasound (EUS) and/or magnetic resonance imaging (MRI)) determines the locoregional staging and optimal treatment for rectal cancer patients. However, for pT1 rectal cancer usually arising into a locally resectable polyp, the yield and role of this diagnostic techniques are no well-established.

Aims & Methods

Aim: To describe the use of locoregional staging and analyze its yield in a pT1CRC state-wide population-based cohort of pT1 rectal cancers.
Patients and methods: Nation-wide population-based cohort, multicenter study (EpiT1Consortium), including 33 centers from 12 different Spanish states. All pT1 CRC cases diagnosed between 2007-2018 were included regardless of the treatment received. Exclusion criteria were: histology other than adenocarcinoma, cancer hereditary syndromes, inflammatory bowel disease, synchronous and metachronous colorectal cancer in the previous 5 years, metastatic neoplastic disease at the time of diagnosis. Information on the demographic of the patient, diagnosis, staging, treatment, complications and histology of pT1 as well as a minimum of 2 years follow-up were collected. Multivariate analysis was performed using binary logistic.

Results

From 3161 patients of the EpiT1 cohort, 681 pT1 rectal cancer with complete information on staging were included for the analysis. 424/681(62.3%) underwent staging: 234(55.2%) with MRI only, 131(30.9%) MRI and EUS, 59(13.9%) only EUS. The characteristics independently associated with the staging (MRI and/or EUS) were: location in lower/middle vs upper rectum (69.1% vs 30.9%; OR 2.8[1.7-4 .5]), suspicion of invasive carcinoma at baseline colonoscopy (64.8% vs 35.2%; OR 2.6[1.6-4.2]), high risk vs low risk histology (69.5% vs 30.5%; OR 2.4[1,3-4,2]), patient management by other specialist (surgeon, oncologist, MDT) vs gastroenterologist (82.7% vs 17.3%; OR 2.2[1.3-3.7]). T staging was correct with MRI in 54/191(28,3%) and with EUS in 69/117(59%) and considering staging by MRI or EUS, 67.1% of patients were over-staged for the T. For N staging considering MRI or EUS the sensitivity and specificity were 15.4% and 82.6%, respectively (Table 1).

Table 1. Diagnostic accuracy for N: in MRI+EUS, only MRI and only EUS

	MRI and EUS		Only MRI		Only EUS
	N+ or recurrence (all therapies) N=82	N+ (oncological surgery) N=39	N+ or recurrence (all therapies) N=243	N+ (oncological surgery) N=122	N+ or recurrence (all therapies) N=121	N+ (oncological surgery) N=49
Sensitivity %	0% (0/2)	0% (0/1)	15,8% (3/19)	16,7% (2/12)	0% (0/6)	0% (0/2)
Specificity %	87,5% (70/80)	78,9% (30/38)	91,1% (204/224)	85,4% (94/110)	96,5% (111/115)	93,6% (44/47)
PPV %	0% (0/10)	0% (0/8)	13% (3/23)	11,1% (2/18)	0% (0/4)	0% (0/3)
NPV %	97,2% (70/72)	96,8% (30/31)	92,7% (204/220)	90,4% (94/104)	94,9% (111/117)	95,6% (44/46)

Conclusion

The limited yield of locoregional staging imaging techniques should be taken into account when choosing the therapeutic strategy of suspected/known T1 rectal cancers. For T staging, considering the high rate of over-staging with imaging modalities, a stepwise approach using histopathology from a local en-bloc resection as a first step seems reasonable. For N staging, a major effort has to be performed to increase the yield of staging modalities in clinical practice.

References

• Toes-Zoutendijk E et al. Gut. 2018 Sep;67(9):1745-1746​​

• Verseveld M et al. Eur J Surg Oncol. 2021 48 (2022):1153-1160​​

• Keys MT et al. Int J Epidemiol. 2021 Mar 3;50(1):143-155​

• ​Benson AB et al . J Natl Compr Canc Netw 2022​​

• Chan et al. Gastrointestinal Endoscopy 2019

Disclosure

No

Introduction

The impact of achieving endoscopic remission in ulcerative proctitis (UP) is unclear. The preferred long-term treatment goal in ulcerative colitis (UC) is achieving both the symptomatic resolution and endoscopic remission (ER),¹ which has been associated with reduced risk of complications, including colectomy.^2,3 UP is an anatomically limited form of UC, involving only the rectum. Unlike in extensive or left-sided UC, UP has not been associated with elevated colorectal cancer risk. Therefore, the achievement of endoscopic healing as compared to clinical remission in UP represents an uncertain therapeutic target.⁴

Aims & Methods

This study assessed the impact of achieving EH on subsequent outcomes in UP patients. This was a single-center retrospective cohort study including patients aged ≥ 18 with a confirmed diagnosis of UP based on clinical and endoscopic criteria. Included patients had at least two endoscopies and active endoscopic disease (Mayo endoscopy score [(MES) of 1, 2, or 3]) at the first (baseline) endoscopy. EH was defined as an MES of 0 or 1 at the second (follow-up) procedure. A minimum time of 1 month between scopes was required for inclusion. Descriptive statistics were used for baseline characteristics. The relationship of EH to IBD-related outcomes was assessed using univariate analysis (Pearson's Chi-squared test; Fisher's exact test; Welch Two Sample t-test) and we identified those independently associated with EH using multivariable logistic regression analysis (odds ratio with 95% confidence interval).

Results

Among 200 UP patients with baseline endoscopic activity, 109 patients (54.5%) achieved EH at follow-up. The median time from baseline to follow-up was 15 months (IQR: 6, 31). EH at follow-up was significantly associated with fewer IBD-related ED visits (healing: 8.3%, no healing: 21%) or hospitalizations (5.5% vs 18%) and fewer GI visits (mean: 8 [SD: 9], vs 17 [22]) after the second scope. Patients with EH were less likely to have iron deficiency anemia (IDA; 23% vs 41%), iron infusion (10% vs 25%), C. difficile infection (0.9% vs 6.6%), or to initiate a new biologic after relapse (15% vs 33%). Patients with EH also had a greater time to clinical relapse (650 days [730] vs 270 days [416]). In multivariable analysis, patients with mucosal healing had 68% lower odds of an IBD-related ED visit (OR: 0.32, 95% CI: 0.13, 0.73), 74% lower odds of IBD-related hospitalization (0.26 [0.09, 0.67]), and 64% lower odds of biologic initiation after relapse (0.36 [0.13, 0.95]) compared to patients with no mucosal healing, adjusting for the index MES score.

	Overall, N = 2001	Healing, N = 1091	No healing, N = 911	P-value2
IBD-Related ED Visit	28 (14%)	9 (8.3%)	19 (21%)	0.01
IBD-Related Hospitalization	22 (11%)	6 (5.5%)	16 (18%)	0.007
Total Number of GI Visits, mean (SD)	12 (17)	8 (9)	17 (22)	<0.001
IDA	62 (31%)	25 (23%)	37 (41%)	0.007
Iron Infusion	34 (17%)	11 (10%)	23 (25%)	0.004
C. Difficile Infection	7 (3.5%)	1 (0.9%)	6 (6.6%)	0.048
Biologic Initiation After Relapse (n=98)	24 (24%)	7 (15%)	17 (33%)	0.034

1 n (%)
2 Pearson's Chi-squared test; Welch Two Sample t-test; Fisher's exact test

Conclusion

UP patients with endoscopic healing had less IBD-related healthcare utilization (ED visits, hospitalizations, GI visits), fewer IBD-related complications (IDA, iron infusion, C. difficile infection), and were less likely to escalate to biologics after relapse. Our findings suggest that using a treatment target of endoscopic healing is desirable in UP and shed light on its potential utility in preventing disease-related complications and improving long-term outcomes.

References

1. Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target. Off J Am Coll Gastroenterol ACG. 2015;110(9):1324-1338. doi:10.1038/ajg.2015.233
2. Colombel JF, Rutgeerts P, Reinisch W, et al. Early Mucosal Healing With Infliximab Is Associated With Improved Long-term Clinical Outcomes in Ulcerative Colitis. Gastroenterology. 2011;141(4):1194-1201. doi:10.1053/j.gastro.2011.06.054
3. Impact of mucosal healing on long‐term outcomes in ulcerative colitis treated with infliximab: a multicenter experience - Laharie - 2013 - Alimentary Pharmacology & Therapeutics - Wiley Online Library. Accessed September 24, 2022. https://onlinelibrary.wiley.com/doi/full/10.1111/apt.12289
4. Zhou Q, Shen ZF, Wu B sheng, et al. Risk of Colorectal Cancer in Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract. 2019;2019:1-11. doi:10.1155/2019/5363261

Disclosure

E.L., A.A.: no conflicts of interest to disclose
R.B.: Consulting/Speaker: Janssen, Abbvie, Bristol Myers Squibb, Prometheus Laboratories, Pfizer, Takeda
R.L.: Consulting/Speaking Fees: Pfizer, Enzymetrics, Ancilia Biosciences. Grant Support: National Institute of Health (NIH)
E.S.: Consulting/Speaking Fees: AbbVie, Crohn’s and Colitis Foundation of America (CCFA), Entera Health, Evidera, GI Health Foundation, Janssen, Protagonist Therapeutics, Seres Health, Takeda Pharmaceuticals, Bristol Myers Squibb. Grant Support: Abbott (AbbVie), AstraZeneca, CCFA, Janssen Research & Development, Johns Hopkins University, National Institute of Diabetes and Digestive and Kidney (NIDDK), National Institute of Health (NIH), New York Crohn’s Foundation, Pfizer, UCB, UCSF–CCFA Clinical Research Alliance, Genentech, Seres Therapeutics, Celgen. R.B.: Consulting: Prometheus
D.L.: Consulting/Speaking Fees: Abbvie, Boehringer Ingelheim, Eli Lilly, Fresenius Kabi, Janssen, Palatin, Pfizer, Prometheus Biosciences, Takeda; Grants: Abbvie, Janssen, Takeda