Introduction

Increased interest in ERCP simulator-based education is driven by the need for efficient and safe endoscopy training in a dedicated environment.
This study assessed whether a structured training program including initial training with the Boškoski-Costamagna ERCP Trainer (BCT) offers benefits to conventional training.

Aims & Methods

This was a one-year prospective, multicenter, parallel-arm, randomized controlled trial involving 16 novice ERCP trainees randomly assigned to study (SG) and control (CG) groups. Both underwent hands-on ERCP training. Additionally, SG had simulator-based training during the first three months. Performance was evaluated with TEESAT score in all ERCPs with any degree of trainee involvement until each trainee completed a minimum of 60 ERCPs. The primary outcome was overall trainee competence rate; secondary outcomes included successful biliary cannulation and adverse event (AE) rates. Learning curves were generated cumulatively over the training period. Both outcomes and the analysis of specific ERCP steps predictive of overall competence were assessed using mixed-effect logistic regression models (MELR). The most effective predictive model of overall competence was identified using a stepwise backward procedure. MELR was employed to investigate potential confounding factors.

Results

1,106 ERCPs were included (SG=562,CG=544). SG trainees demonstrated higher success in native biliary cannulation (SG=52%, CG=42%, p<0.001), achieved faster biliary cannulation [SG=3(6)min, CG=5(8)min, p<0.001], and showed a faster evolution on overall performance, native biliary cannulation, and sphincterotomy. Successful biliary cannulation [OR=10.10, 95% CI (5.15-19.83)] and sphincterotomy [OR=7.71, 95% CI (3.77-15.76)] were the most important predictors for overall competence. The multivariate random-effects model demonstrated an almost significant association between simulator-based training [OR=3.24, 95% CI (1.01-10.39), p=0.049] and overall competence, accounting for biliary cannulation, sphincterotomy, and stone removal. No confounding factors were identified.

Conclusion

This study suggests that early simulator training with BCT accelerates the learning curve of trainees in performing key steps of the ERCP procedure and improves overall competence as assessed by dedicated tools during ERCP training.

Introduction

Colonoscopic surveillance reduces colorectal cancer (CRC) incidence and mortality in Lynch syndrome (LS) carriers. Still, its invasiveness and high costs highlight the need for a non-invasive approach to predict the presence of neoplastic lesions.

Aims & Methods

This study aimed to identify faecal bacterial biomarkers to discern between carriers with colorectal lesions and those with normal colon.
Two independent Spanish cohorts (a training and a validation cohort) were recruited through two multicenter studies (Table 1). Participants provided a faecal sample before surveillance colonoscopy to quantify the abundance of F. prausnitzii (FPRA) and its phylogroups I and II (PHGI and PHGII), P. stomatis (PTST), B. fragilis (BCTF), B. thetaiotaomicron (BCTT), B46 (best BLAST match S. variabile), G. morbillorum (GMLL), B48 (best BLAST match R. faecis), and E. coli (ECO) through qPCR. Eubacteria (EUB) was quantified as the total bacterial load. Participants were classified based on colonoscopy findings as normal colonoscopy (NC), non-advanced adenoma (NAA), and advanced neoplasia (AN, including advanced adenoma and CRC). A bacterial signature for neoplasia prediction was defined and validated in the training and validation cohorts, respectively.

Table 1. Main characteristics of the study participants. NC, normal colonoscopy; NAA, non-advanced adenoma; AA, advanced adenoma; CRC, colorectal cancer.

Results

The bacterial abundances were analysed in the training cohort according to age, sex, body mass index (BMI), germline mutation, and colonoscopy findings. Significant moderate positive correlations were identified between the abundances of BCTF and age (r=0.325, p=0.040), and PHGII and BMI (r=0.399, p=0.010). A significant negative correlation was identified between GMLL abundance and BMI (r=-0.331, p=0.036). Patients harbouring MLH1 mutations exhibited a significantly higher abundance of FPRA compared to PMS2 carriers (p=0.048). Patients with neoplasia (NAA+AN) presented significantly lower abundances of BCTF (p=0.027) and B48 (p=0.038) than patients with NC. Patients with AN presented a significantly lower abundance of PTST compared to patients with NC or NAA (p=0.032).
Although all the bacterial markers achieved a sensitivity of 100% to predict the presence of neoplasia, none of them presented a specificity higher than 25% by itself. To maintain sensitivity and increase specificity a bacterial signature was defined including ECO, BCTF, GMLL, FPRA, PHGI, PHGII, and B46 combined with the inherited mutation. The signature showed 100% sensitivity (SS), 52.50% specificity (SP), 34.48% positive predictive value (PPV), and 100% negative predictive value (NPV). This signature was subsequently validated demonstrating 100% SS, 56.45% SP, 53.44% PPV, and 100% NPV.

Conclusion

A new faecal bacterial signature to predict the presence of colorectal neoplasia in LS carriers has been identified, showcasing its potential usefulness to improve and personalise LS surveillance, optimising endoscopic resources, and providing a less invasive and cost-effective approach.

Disclosure

S. Taboada-López, M. Malagón, S. Ramió-Pujol and M. Serra-Pagès are employees of GoodGut.

Clinical Case Summary

Gastrointestinal tuberculosis (GITB) is an uncommon form of extrapulmonary tuberculosis that poses a diagnostic challenge due to its non-specific clinical presentation. Among its varied manifestations, gastrointestinal bleeding as an initial presentation is exceedingly rare. This case report aims to highlight the diagnostic difficulties, treatment modalities, and clinical outcomes in a patient with GITB presenting as gastrointestinal bleeding.
This is a case of a 24/M, no known comorbidities, immunocompetent host, no maintenance medications who came in for sudden onset of hematochezia with progressive drop in hemoglobin levels. Work up revealed a circumferential wall thickening involving the ileocecal region. Bleeding from mass was difficult to control despite medications and colonoscopy attempts hence patient underwent exploratory Laparotomy, right segmental colectomy. Histopathology results revealed caseating chronic granulomatous inflammation and lymph nodes showing caseating granulomas. Patient was then started on anti-Kochs treatment with note of improvement of symptoms post treatment.

References

1. Sharma, V., Mandavdhare, H. S., Lamoria, S., & Dutta, U. (2019). Gastrointestinal tuberculosis: A systematic review and meta-analysis. Scandinavian Journal of Gastroenterology, 54(5), 567-577. doi:10.1080/00365521.2019.1598343
2. Kapoor, A., & Schewitz, I. (2020). Gastrointestinal tuberculosis: Understanding the molecular mechanisms for better diagnosis and treatment. Journal of Digestive Diseases, 21(4), 195-204. doi:10.1111/1751-2980.12866
3. Amarapurkar, D. N., Patel, N. D., & Amarapurkar, A. D. (2018). Gastrointestinal tuberculosis. Indian Journal of Medical Research, 147(5), 401-416. doi:10.4103/ijmr.IJMR_1004_17
4. Sharma, V., Mandavdhare, H. S., & Lamoria, S. (2020). Update on gastrointestinal tuberculosis: Newer techniques and treatment strategies. World Journal of Gastrointestinal Pharmacology and Therapeutics, 11(3), 10-26. doi:10.4292/wjgpt.v11.i3.10

Disclosure

None

Clinical Case Summary

Leiomyomas are benign soft tissue neoplasms that arise from smooth muscle. They are uncommon in the colon. We report two cases of colonic sessile polyps that underwent polypectomy and histology showed leiomyoma.

The first patient previously had a history of polyps with tubular adenoma with low grade dysplasia. A repeat colonoscopy for polyp surveillance was done which found polyps in the ascending colon, and sigmoid. The sigmoid colon polyp was 4mm in size and removed via cold snare polypectomy (Figure 1).
The second patient had underlying non-alcoholic fatty liver disease cirrhosis and iron deficiency anaemia. Colonoscopy showed colonic polyps which were biopsied (Figure 2).

The histology of the first patient’s sigmoid colon polyp showed nodular spindle cell lesion centered in the submucosa/muscularis mucosa. The lesion was composed of spindle cells in fascicles with bland spindled nuclei and eosinophilic cytoplasm. Desmin and SMA stains were done and they were diffusely positive. CD117 stains were negative. DOG1 showed focal nonspecific staining in lesional cells. The overlying lamina propria also showed aggregates of foamy histiocytes and lymphoid aggregates. These were consistent with a leiomyoma.
The second patient’s histology also showed fascicles of spindle cells and immunohistochemistry stain showed positivity for SMA and desmin but negative for CD117 and DOG-1, consistent with leiomyoma.

As the polyps showed smooth margins endoscopically and has similar appearance to hyperplastic polyps, it was likely thought to have a hyperplastic component on top of leiomyoma, hence the patients are to be monitored and followed up for routine surveillance.

References

Miettinen M, Sobin LH, Am J Surg Pathol. 2001;25(11):1433

Introduction

The asymptomatic nature of precancerous lesions, namely low- and high-grade dysplasia (LGD and HGD, respectively), constitutes a major clinical challenge that precludes a timely detection of gastric cancer (GC) in curable stages. The identification of novel and accurate biomarkers holds the promise of a better risk assessment and citizens stratification for an early diagnosis. In this exploratory study, we proposed to characterize the transcriptomic landscape of gastric lesions (GL) towards the definition of a molecular profile for early screening of GC in Western populations.

Aims & Methods

RNA-Sequencing analysis was conducted on RNA extracted from 39 formalin-fixed paraffin-embedded (FFPE) samples: 20 “normal-appearing” mucosa controls and 19 gastric lesions (GL), including LGD, HGD, and adenocarcinoma. Differential expression analysis, functional enrichment analysis, least absolute shrinkage and selection operator (Lasso) regression, and the machine-learning extreme gradient boosting (XGBoost) algorithm were employed to identify potential biomarkers and assess the predictive value of the molecular signature of the top dysregulated genes.

Results

A total of 1171 differentially expressed genes (DEGs) were identified in GL. Remarkably, 867 of these genes (74%) showed exclusive dysregulation in lesions compared to stage I GC samples from The Cancer Genome Atlas (TCGA) stomach adenocarcinoma (STAD) cohort. These unique biomarkers predominantly participate in translation, as well as metabolic and biosynthetic processes. In contrast, DEGs from TCGA-STAD cohort were primarily enriched in immunity-related processes. Notably, the eight best genes model, comprising ADAMTSL1, CLDN2, ENC1, GSR, IQNC, PER1, PRR33, and a novel transcript corresponding to a long non-coding RNA (lncRNA, ENSG00000227218), achieved an area under the curve (AUC) of 0.938 (95% CI: 0.815-1.000), with a sensitivity of 87.5% and specificity of 100% to classify GL samples.

Conclusion

This preliminary study identified over 800 DEGs exclusively in GL compared to stage I GC. Moreover, it unveiled a molecular-based signature that effectively discriminates patients with GL in an intermediate-risk population. This discovery paves the way for enhancing early GC screening strategies, particularly for those who can be treated through minimally invasive, nonsurgical procedures.

Introduction

Filgotinib (FIL) is an oral, JAK1 preferential inhibitor approved for the treatment of ulcerative colitis (UC). Although the clinical efficacy of FIL in UC has been demonstrated in the SELECTION trial,¹ real-world data are limited.

Aims & Methods

In total, 600 adult patients with moderately to severely active UC who initiate FIL treatment in routine clinical care will be enrolled in GALOCEAN (NCT05817942), an ongoing, European, multi-site, prospective, observational study. Here, we report baseline characteristics of the first 100 enrolled patients and effectiveness data from patients who reached week 10. Baseline demographics, disease characteristics, prior UC-related treatment and reasons for starting FIL were collected. At week 10, mean changes from baseline (CFBs) in the partial Mayo Clinic Score (pMCS) and the PRO-2 score, and the proportions of patients in pMCS remission (pMCS of ≤2) or PRO-2 remission (rectal bleeding subscore of 0 and stool frequency subscore of ≤1) were assessed. Mean CFBs at week 10 in patient-reported outcomes (Short Inflammatory Bowel Disease Questionnaire [SIBDQ], Urgency Numerical Rating Scale [NRS] and Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue] scores) were also calculated. Safety was evaluated by documenting adverse events.

Results

As of January 2024, 100 patients (FIL 200 mg, 97% [97/100]; FIL 100 mg, 3% [3/100]) were enrolled, and had baseline data available; out of which 55 reached week 10. Baseline characteristics are shown in the Table. In total, 70% of patients (67/96) had up to moderate disease activity (pMCS of ≤6) and 30% (29/96) had severe disease activity (pMCS of ≥7) at baseline; 42% (42/100) were biologic-naive. The most common cardiovascular risk factor was active or prior smoking (37% [37/100]). FIL was used as monotherapy in 47% of patients (47/100). At week 10, the mean (standard deviation [SD]) CFB in the pMCS was –2.7 (2.5; n=43), and 58% of patients (25/43) achieved pMCS remission. The mean (SD) CFB in the PRO-2 score at week 10 was –1.8 (1.7; n=46), and 72% of patients (33/46) achieved PRO-2 remission. Mean (SD) CFBs in patient-reported outcomes at week 10 were 10.1 (12.4; n=42) for the SIBDQ score, –1.3 (2.8; n=38) for the Urgency NRS score and 4.0 (9.3; n=42) for the FACIT-Fatigue score. Overall, 10 patients discontinued FIL because of adverse events, lack of effectiveness or physician decision. No new safety signals were identified.

Conclusion

In this first interim report of GALOCEAN, week 10 data show that FIL improves symptoms in patients with UC in real-world clinical practice and has beneficial effects on health-related quality of life and fatigue. GALOCEAN is ongoing and long-term data with higher patient numbers will be evaluated to further characterize the real-world effectiveness of FIL in UC.

Table. Baseline characteristics.

References

1. Feagan BG et al. Lancet 2021;397:2372–84.

Disclosure

The GALOCEAN study was sponsored by Galapagos NV (Mechelen, Belgium), who funded these analyses.
Medical writing support for the development of this abstract was provided by Risha Bulusu, MBiochem, of PharmaGenesis London, London, UK, and was funded by Alfasigma S.p.A.
WS, AM, MZ are employees of Alfasigma S.p.A at the time of abstract submission.
AA reports consulting and/or advisory board fees from AbbVie, Allergan, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Gilead Sciences, Janssen Pharmaceuticals, Lionhealth, MSD, Mylan, Nestlé, Pfizer, Roche, Samsung Bioepis, Sandoz and Takeda; lecture and/or speaker bureau fees from AbbVie, Amgen, Biogen, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Gilead Sciences, Janssen Pharmaceuticals, Mitsubishi Tanabe Pharma Corporation, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda and Teva Pharmaceuticals; and research grants from Biogen, MSD, Pfizer and Takeda.
CGdSJ reports speaker and/or consultancy fees from AbbVie, Alfasigma, Amgen, Celltrion, Janssen, Galapagos, MSD, Pfizer and Takeda.
ER reports speaker fees from AbbVie, Faes Farma, Ferring Pharmaceuticals, Galapagos, Janssen Pharmaceuticals, Kern Pharma, MSD, Pfizer and Takeda; and consulting fees from AbbVie, Eli Lilly, Fresenius Kabi, Galapagos, Janssen Pharmaceuticals, MSD and Pfizer.
GD reports research/educational grants from Abbott, AbbVie, Celltrion, Genuity, Janssen Pharmaceuticals, MSD, Pfizer, Takeda and Tillotts Pharma; and speaker/personal fees from AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Dr Falk Pharma, Galapagos, Gilead Sciences, Janssen Pharmaceuticals, MSD, Pfizer, Takeda/Shire and Tillotts Pharma.
JPS reports speaker fees from AbbVie, Fresenius Kabi, Galapagos, Janssen-Cilag, Pharmacosmos, Takeda and Tillotts Pharma; and advisory board fees from AbbVie, Bristol Myers Squibb, Dr Falk Pharma and Galapagos.
ML reports consultancy/lecture fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Galapagos, Janssen-Cilag, Johnson & Johnson, Medtronic, Pfizer, Takeda, and Tillotts, grants from
Galapagos and NFU and central reading services for Alimentiv.
MLH reports research grants from Ferring, Janssen, Pfizer, Tilllotts, and Takeda, speaker fees from AbbVie, Ferring, Galapagos, Meda, MSD, Tilllotts and Takeda; and advisory board fees from AbbVie, Eli Lilly, Galapagos, Janssen, MSD, Pfizer and Takeda.
RS reports no financial disclosures or conflicts of interest.
SV reports financial support for research from AbbVie, Galapagos, Johnson & Johnson, Pfizer and Takeda; speaker and/or consultancy fees from AbbVie, Abivax, AbolerIS Pharma, AgomAb Therapeutics, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Bior Therapeutics (formerly Progenity), Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cytoki Pharma, Dr Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Genentech-Roche, Gilead Sciences, GSK, Hospira, IMIDomics, Janssen Pharmaceuticals, Johnson & Johnson, Materia Prima, Mestag Therapeutics, MiroBio, Morphic Therapeutic, MRM Health, MSD, Mundipharma, Pfizer, ProDigest, Prometheus Biosciences, Robarts Clinical Trials, Surrozen, Takeda, Theravance Biopharma, Tillotts Pharma AG, VectivBio, Ventyx Biosciences and Zealand Pharma.
SS reports personal fees from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos/Gilead Sciences, Hikma Pharmaceuticals, I-Mab, Janssen Pharmaceuticals, Morphic Therapeutic, MSD, Mylan, Pfizer, Protagonist Therapeutics, Provention Bio, Sandoz/Hexal, Takeda, Theravance Biopharma and Ventyx Biosciences.
WR reports speaker fees from AbbVie, Celltrion, Ferring Pharmaceuticals, Galapagos, Janssen Pharmaceuticals, MEDICE, MSD, Pfizer, Roche, Sobi and Takeda; consulting fees from AbbVie, Amgen, AOP Health (formerly AOP Orphan), Boehringer Ingelheim, Bristol Myers Squibb, Calyx, Celltrion, Eli Lilly, Galapagos, Gilead Sciences, InDex Pharmaceuticals, Janssen Pharmaceuticals, MedAhead, Microbiotica, Pfizer and Takeda; advisory board fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Galapagos, Janssen Pharmaceuticals and Pfizer; and research funding from AbbVie, Janssen Pharmaceuticals, Sandoz, Sanofi and Takeda.
AJ and WS were employees of Galapagos NV (former study sponsor), and are now employees of Alfasigma S.p.A (current study sponsor).
MZ was an employee and shareholder of Galapagos NV (former study sponsor), and is now an employee of Alfasigma S.p.A (current study sponsor).

Introduction

Resection of large non-pedunculated colorectal polyps (LNPCP) located in the rectum varies by institution and region with some, particularly colorectal surgeons, favouring TEM and others endoscopic resection (ER). There is a paucity of data directly comparing these strategies and the procedure of choice remains under debate. Our unit is a tertiary referral centre for complex polyps and early colorectal cancer. All rectal LNPCP were treated by TEM until a change in practice from 2011 when the first-line therapeutic strategy for rectal LNPCP changed to ER.

Aims & Methods

We aimed to report the outcomes of TEM and ER of rectal LNPCP from a large tertiary cohort. Large (≥20mm) rectal adenomas resected by TEM or ER (2009 – 2023) were analysed. From 2009-2011 all rectal adenomas were treated by TEM, after which the primary resection strategy changed to ER. Outcomes were compared between techniques. Given the difference in resection strategy, a composite outcome of septic complications included clinically significant perforation for ER (early or delayed perforation requiring any form of unplanned medical or surgical treatment) and septic complications for TEM (peritonitis or pelvic/anorectal sepsis).

Results

704 rectal adenomas were resected by TEM (n=71), EMR (n=145) and ESD/Hybrid ESD (n=488) with a mean size of 45mm for TEM vs 55mm for ER (p<0.001). 100% of patients undergoing TEM required hospital admission vs 15% for ER (p<0.001), and 100% required general anaesthesia (GA) for TEM vs 26%% for ER (GA or propofol sedation, p<0.001). En bloc resection was achieved for 96% of ESD resections, 54% of TEMS, 28% of EMR and 14% of hybrid ESD (p<0.001). The incidence of complications were similar (9.9% for TEM versus 5.0% for ER, p=0.10). Recurrence occurred in 2.7% after ESD, 21.1% after EMR, 23.6% after Hybrid ESD and 36.4% after TEM (p<0.001). No patients undergoing ER or TEM required surgery as a result of a complication.

Conclusion

Despite significantly larger lesion sizes, ER in our institution provides far superior results for patients than TEM with relatively fewer patients requiring hospital admission and lower recurrence rates, especially with ESD. En bloc resection was more likely with ER as a result of the difficulty achieving en bloc resection for extremely large lesions with TEM, which can invariably be resected en bloc by ESD. These results have led to a policy of ER for all apparently benign rectal tumours regardless of size and, in recent years, ESD as the primary approach for all rectal lesions.