Introduction

EMR is the standard of care for the management of large (≥20mm) non-pedunculated colonic polyps (LNPCPs). However, its efficacy and cost effectiveness, are limited by recurrence and the necessity for scheduled surveillance. Consequently, current surveillance intervals are conservative. Margin thermal ablation (MTA) after EMR for LNPCPs has dramatically reduced the incidence of recurrence at first surveillance colonoscopy at six-months (SC1). If this effect is durable, then subsequent surveillance intervals in patients who have been cleared of synchronous polyps could be substantially lengthened. We prospectively evaluated long-term surveillance outcomes in a cohort of LNPCPs that have undergone MTA.

Aims & Methods

Consecutive patients with LNPCPs undergoing EMR and MTA from four academic endoscopy centres were prospectively recruited. All patients that underwent successful endoscopic resection received SC1 six months post resection. EMR scars were carefully evaluated with high-definition white light, narrow band imaging with near focus and biopsy. In the absence of recurrence, second surveillance (SC2) colonoscopy was conducted at a subsequent interval of 12 months with the scar evaluation process repeated. The primary outcome was recurrence at SC2 in all LNPCPs with a recurrence-free scar at SC1.

Results

1324 LNPCPs referred for EMR were enrolled over 90 months until October 2022. Following exclusions, 1163 LNPCPs underwent EMR with complete MTA. 856 LNPCPs underwent SC1. 32 additional synchronous LNPCPs were cleared at this procedure. 25/856 (2.9%) (95%CI 1.9-4.3%) LNPCPs demonstrated recurrence. 469 LNPCPs free of recurrence at SC1 (median size 35mm) underwent SC2 at a mean interval of 22.9 months (95%CI 21.9-23.95) after the index EMR. 468 demonstrated a bland scar without recurrence. Only one recurrence occurred (0.2% 95%CI 0-1.2%), related to a 0-IIa+Is 20mm granular TVA located on the ileocaecal valve.

Conclusion

LNPCPs that have undergone successful EMR with MTA and are free of recurrence at SC1 are very unlikely to develop recurrence in subsequent surveillance out to 2 years. Following EMR of LNPCPs with MTA, patients who are cleared of synchronous neoplasia and demonstrate no recurrence after careful scar examination, can potentially undergo next surveillance in 3-5 years. Such an approach would reduce costs and enhance patient compliance.

Disclosure

Michael Bourke: Research Support: Olympus Medical, Cook Medical, Boston Scientific
The remaining authors have no financial, professional, or personal conflicts of interest to disclose

Introduction

Ulcerative colitis (UC) is characterized by chronic immune mediated inflammation of the colon and rectum. Corticosteroid (CS) is a common treatment for patients with moderate to severe active UC, but its effect varies among patients, including resistance, response, and dependence. In addition, the longer CS therapy continues, the greater the concern regarding drug-related adverse effects. New immunomodulatory therapies are being developed for the treatment of UC drug showing promise in the treatment of patients with moderate UC refractory to aminosalicylic acid (5-ASA). Thus, the clinical benefit of being able to predict whether certain patients would benefit from CS therapy prior to administration cannot be overestimated.

Aims & Methods

We compared the clinical characteristics of patients with steroid-responder (SR) and steroid-non-responder (SNR) UC and retrospectively evaluated for biomarkers that could predict the efficacy of CS prior to administration in patients with moderate to severe active UC who failed to respond to 5-ASA.
We enrolled 100 UC patients presenting at Nippon Medical School Hospital with a history of CS administration prior to December 2023. The patients were divided into two groups, SR patients and SNR patients, and their clinical characteristics were determined according to medical records. Eosinophil counts were measured in the high-power field using Direct Fast Scarlet staining.

Results

Clinical characteristics of UC patients were as follows: the median age, 48±17 years; height 167±9.2 cm, and weight, 58±14 kg; including 61 males to 39 females. The most common disease extent type was the total colitis (63%), followed by left-sided colitis (32%), and proctitis (5%). Complete SNR was observed in 15 patients (15%), with remaining 85 patients (85%) classified as SR. There was no significant difference found in Mayo Endoscopic Score, first dose of CS, number of hospitalizations, number of relapses, propotion of patients with total-colitis type, or duration of CS treatment between the SR group and the SNR group. The non-remission rate, defined as failure to achieve mucosal healing, was significantly higher in the SNR group (66%) than in the SR group (36%) (P=0.03). The proportion of patients treated with azathioprine was significantly higher in the SR group (40%) than in the SNR group (39%). The proportion of patients treated with biologics or small molecular compounds was significantly higher in the SNR group (40%) than in the SR group (22%) (P=0.03).
We then compared hematological biomarkers in blood samples obtained prior to CS administration between the two groups. There was no significant difference in WBC counts, hemoglobin values, serum albumin concentrations, CRP values, and ESR between the two groups. However, eosinophil profiles (both total count numbers and ratio to white blood cell counts) were significantly higher in the SR group than in the SNR group (P=0.02). Neutrophil-lymphocyte ratio tended to be higher in the SR group than in the SNR group (P=0.06). The number of infiltrated eosinophils in the inflamed rectal mucosal tissue was not significantly different between the two groups. The number of infiltrated eosinophils in the rectal mucosa tended to decrease in the steroid-response groups (p = 0.07). However, there was no difference in the number of infiltrated eosinophils in the steroid-non-response groups.

Conclusion

Both eosinophil in the blood and in the rectal mucosa, and neutrophil-lymphocyte ratio in the blood could be potential biomarkers for steroid responsiveness prior to administration.

References

・British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019; 68: s1–s106
・Severe ulcerative colitis: at what point should we define resistance to steroids? WJG 2008 Sep 28;14(36):5504-7.
・A reproducible grading scale for histological assessment of inflammation in ulcerative colitis: Gut 47：404－409，2000
・Mucosal Eosinophil Abundance in Non-Inflamed Colonic Tissue Is Associated with Response to Vedolizumab Induction Therapy in Inflammatory Bowel Disease：J Clin Med Res,2022

Introduction

Adequacy of bowel preparation (ABP) directly affects colonoscopy performance and adenoma detection rate. Studies attributed a role to the dosing regimen of the bowel cleansing agent, social and economic factors and comorbidities. However, data on the impact of kidney failure and renal replacement therapy (RRT) are lacking.

Aims & Methods

This study investigated how ABP compares between patients on RRT and age-matched subjects with normal kidney function.
All patients on RRT undergoing an elective colonoscopy between January 2016 and December 2021 were identified from the medical records of a university hospital, and matched to 2 closest age controls undergoing colonoscopy at the same date ± 7 days. Study subjects and controls were compared for demographics, comorbidities including history of abdominal surgery, use of bowel transit-influencing drugs, residential care stay and colonoscopy-related data (bowel preparation regimen, sedation type, colonoscopy findings, ABP defined as a cumulative Bristol Bowel Preparation Score >= 6 and a score of >= 2 for each colon segment). Statistical significant contributors to ABP were assessed by logistic regression.

Results

Ninety-one patients on RRT (76 on haemodialysis and 15 on peritoneal dialysis) and 182 controls were identified. Patients on RRT were older (69±12 vs. 64±14y, p=.008) and less frequently women (34% vs. 50%, p=.013). They had more diabetes (40% vs. 24%, p=.008), more history of abdominal surgery (32% vs. 21%, p=.047) and took more bowel transit-influencing drugs (50% vs. 28%, p<.0001). Bowel preparation regimens were equally distributed between both groups. There was no difference in the rate of ABP between groups (87% vs. 81%, p=NS). Logistic regression analysis did not reveal an association between RRT and ABP. ABP was negatively influenced by residency in residential care, overnight stay in the hospital before colonoscopy, history of central nervous system disease, and positively by split-dose regimen (Nagelkerke R square 0.329, p=<.001).

Conclusion

Despite less favourable associated conditions, ABP in RRT patients remains comparable to controls. Split-dose regimen, neurological conditions and in-hospital stay are significant predictors of adequate bowel preparation.

References

Clark BT, Rustagi T, Laine L. What level of bowel prep quality requires early repeat colonoscopy: systematic review and meta-analysis of the impact of preparation quality on adenoma detection rate. Am J Gastroenterol. 2014;109(11):1714-23; quiz 24.
Hassan C, East J, Radaelli F, Spada C, Benamouzig R, Bisschops R, et al. Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2019. Endoscopy. 2019;51(8):775-94.
Saumoy M, Jesudian AB, Aden B, Serur D, Sundararajan S, Sivananthan G, et al. High prevalence of colon adenomas in end-stage kidney disease patients on hemodialysis undergoing renal transplant evaluation. Clin Transplant. 2016;30(3):256-62.
24. Calderwood AH, Schroy PC, 3rd, Lieberman DA, Logan JR, Zurfluh M, Jacobson BC. Boston Bowel Preparation Scale scores provide a standardized definition of adequate for describing bowel cleanliness. Gastrointest Endosc. 2014;80(2):269-76.
25. Clark BT, Protiva P, Nagar A, Imaeda A, Ciarleglio MM, Deng Y, et al. Quantification of Adequate Bowel Preparation for Screening or Surveillance Colonoscopy in Men. Gastroenterology. 2016;150(2):396-405; quiz e14-5.
artel M, Barkun AN, Menard C, Restellini S, Kherad O, Vanasse A. Split-Dose Preparations Are Superior to Day-Before Bowel Cleansing Regimens: A Meta-analysis. Gastroenterology. 2015;149(1):79-88

Introduction

Inflammatory Bowel Diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract, characterized by a relapsing-remitting course, primarily comprising Ulcerative Colitis (UC) and Crohn’s Disease (CD). These conditions, which lack a clearly defined cause, pose significant interest to the medical community for identifying reliable predictors of disease progression and treatment response.
The specific profile of extrachromosomal circular DNA fragments (eccDNA) has emerged as a promising diagnostic and prognostic biomarker for various types of cancer. However, their role in IBD patients, including the specific gene fragments they carry, has not been thoroughly investigated so far.

Aims & Methods

This monocentric, observational, case-controlled study enrolled consecutive patients diagnosed with IBD and non-IBD healthy controls undergoing colonoscopy for colorectal cancer screening at Fondazione Policlinico Universitario “A: Gemelli”. Disease activity in IBD patients was assessed using different scoring systems: the Partial Mayo Score (PMS) and Mayo Endoscopic Subscore (MES) for UC, and the Harvey-Bradshaw Index (HBI) and Simple Endoscopic Score for CD (SES-CD) for CD. Colonic biopsies were obtained from both inflamed and healthy mucosa of IBD patients and from non-IBD controls. Purification of human eccDNA was optimized according to the Circle-Seq method, including eccDNA enrichment, removal of linear and mitochondrial DNA, rolling-circle amplification and sequencing; subsequently, eccDNAs were identified using Circle Finder software. The study compared the relative abundances of genes within eccDNAs between IBD patients and non-IBD controls, focusing on those that were differentially abundant, defined as Differentially Produced per Gene eccDNAs (DPpGCs).

Results

133 patients with IBD (69 with CD, 64 with UC) and 17 healthy controls (HC) were included in the study. Colonic mucosal samples from IBD patients revealed a higher average abundance of eccDNAs compared to samples from HC. This increase was consistent across all chromosomes, suggesting a global upregulation of eccDNA production throughout the human genome. Furthermore, there was a slight yet statistically significant trend towards larger eccDNAs sizes in IBD patients compared to HC. Even when considering only eccDNA derived from genic elements ("genic eccDNAs"), IBD patients exhibited a significantly higher abundance of eccDNA in the gut compared to non-IBD controls.
Further analysis focused on DPpGCs with a fold change >1 log2 between IBD patients and HC, with a significance threshold of p < 0.01. Forty-nine genes were found to be enriched in IBD patients, including GRID2 and NRG3. Similarly, in CD patients, 176 genes, such as FGF14, SOX5, and ZBTB20, were significantly enriched compared to HC. In UC patients, 31 genes, including NRG1, SPOCK3, and ATP13A4, showed enrichment compared to HC. Moreover, IBD patients in endoscopic remission (SES-CD < 3, EMS of 0-1) tended to have fewer eccDNAs in their intestines compared to those with active disease, although this difference did not reach statistical significance. Five DPpGCs, including FARS2, HERC3, and PNK2, were identified when applying the aforementioned criteria.

Conclusion

In conclusion, our study unveils a distinct pattern of eccDNA production specific to IBD. We showed that circles harboring specific genes can distinguish UC and CD from healthy controls with statistical significance (p < 0.01). We suggest that eccDNA identification may serve as a novel diagnostic biomarker for IBD patients.

Introduction

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by esophageal dysfunction and a peak eosinophil count of >15 cells per high power field (HPF). Recent studies suggest that mast cells play a key role in its pathophysiology. This study investigates the presence of mast cells in different groups of patients with EoE.

Aims & Methods

Biopsy samples from patients newly diagnosed with EoE were analyzed, and the Eosinophilic Esophagitis Histology Scoring System (EOEHSS) grade and stage scores were calculated. Biopsy samples were divided in two groups: t0 (before the starting of EoE therapy) and t1 (after EoE therapy). Mast cells were detected using tryptase immunohistochemistry, and the maximum number of mast cells counted in a high-power field (PMC), was recorded. Univariate correlation analysis were performed between PMC and peak eosinophil count (PEC), PMC and EOEHSS grade, PMC and EOEHSS stage, PMC and EREFS.

Results

12 patients affected by EoE were divided in group 1, treated with PPIs [Esomeprazole 40 mg, bis in die (bid)] and group 2, treated with BOT (budesonide oral tablets 1 mg, bid). Univariate correlation analysis were performed at t0 and t1. Results from Pearson’s R for analysis at t0 are showed a positive linear correlation in PEC-PMC (0,567, p=0,043) and EOEHSS grade-PMC (0,559, p=0,047). At t1, EREFS-PMC had a positive correlation (0,726, p 0,005), like also EOEHSS grade-PMC (0,74, p=0,002) and EOEHSS stage-PMC (0,818, p<0,001).

Conclusion

PCM positively correlates with PEC, EOEHSS grade, EOEHSS stage and EREFS in untreated samples, supporting their role in EoE and type-2 inflammation. In treated cases, PMC correlate with PEC, EOEHSS grade, EREFS. A highly statistically significant strong positive linear correlation was found between PMC and EOEHSS stage, as the latter is more likely to reflect the whole esophageal histologic changes.
Our study suggests that mast cell count, alongside eosinophil counts, could be an important factor in evaluating anti-inflammatory therapeutic interventions and it may be a useful adjunct to existing endoscopic and histologic markers in assessing EoE severity, supporting their role in EoE and type-2 inflammation. To confirm these findings, further longitudinal prospective studies are required.

References

N. de Bortoli, P. Visaggi, R. Penagini et al., The 1st EoETALY consensus on the diagnosis and management of eosinophilic esophagitis – Definition, clinical presentation and diagnosis, Digestive and Liver Disease
Collins MH, et al. Eosinophilic esophagitis histology remission score: significant relations to measures of disease activity and symptoms. J. Pediatr. Gastroenterol. Nutr. 2020;70(5):598–603
Kanamori A, et al. Esophageal mast cells may be associated with the perception of symptoms in patients with eosinophilic esophagitis. Esophagus. 2023 Apr;20(2):333-341
Bolton SM, et al. Mast Cell Infiltration Is Associated With Persistent Symptoms and Endoscopic Abnormalities Despite Resolution of Eosinophilia in Pediatric Eosinophilic Esophagitis. Am J Gastroenterol. 2020 Feb;115(2):224-233.

Introduction

Inflammatory Bowel Disease (IBD), encompassing Crohn's Disease (CD) and Ulcerative Colitis (UC), shares chronic and inflammatory characteristics with Non-Alcoholic Fatty Liver Disease (NAFLD). While their precise pathogenesis remains unclear, emerging evidence implicates dysbiosis and metabolic changes. This study aims to investigate the association between IBD and NAFLD, focusing on metabolic syndrome and its nutritional implications

Aims & Methods

Objective: To evaluate the nutritional status and body composition in IBD patients, comparing groups with and without NAFLD, and identifying the associated factors.
Methods: A cross-sectional study was conducted, assessing clinical data, metabolic syndrome presence, nutritional status, and biochemical markers. Patients were categorized into IBD+NAFLD and IBD-only groups based on hepatic ultrasound findings. Statistical analysis included descriptive statistics and logistic regression.

Results

127 patients were included, comprising 58 CD and 69 UC, with a mean age of 45.56 years. Most patients were female and did not engage in physical activity. Patients were mostly in clinical remission and endoscopic activity. 58 patients (45.67%) had hepatic steatosis on ultrasound, forming the IBD+NAFLD group. The IBD+NAFLD group had higher BMI, fat mass, and all circumference values, Table 1, as well as a higher prevalence of hypertension (p=0.0446) and dyslipidemia (p=0.0377). It is noteworthy that, although most of these patients were classified as overweight by BMI, considering anthropometric data, most IBD+NAFLD patients were classified as eutrophic. 86.21% of patients in the IBD+NAFLD group met the criteria for MAFLD. No difference was observed regarding medication in use. Regarding biochemical tests, the IBD+NAFLD group had higher values of hematocrit (p=0.0023), liver enzymes (AST, p=0.0141 and ALT, p<0.0001), fasting glucose (p=0.0107), glycated hemoglobin (p=0.0146), basal insulin (p=0.0003), and triglycerides (p=0.0001), with lower HDL cholesterol (p=0.0101)

Conclusion

The study highlights a significant association between nutritional status and NAFLD in IBD patients. Those categorized as eutrophic had a higher prevalence of hepatic steatosis, potentially linked to dietary factors.

References

Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and
natural history of non‐alcoholic fatty liver disease and non‐alcoholic
steatohepatitis in adults. Alimentary pharmacology & therapeutics.
2011;34(3):274-285./ Silva A.F; Schieferdecker M.H; Amarante M. B. Ingestão alimentar em pacientes
com doença inflamatória intestinal ABCD, arq. bras. cir. dig. 24 (3) • Set 2011/ Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA.
2015;313(22):2263-73

Introduction

Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needle has a high diagnostic accuracy and enables physicians to obtain sufficient pathological samples compared to standard needles ^1-2. However, no conclusion has been reached regarding the best combination of the number of passes and the number of to-and-fro movements (TAFs) in EUS-FNB. Although adverse events associated with EUS-FNB are rare, serious bleeding and tumor dissemination can occur ³.

Aims & Methods

Fewer passes and TAFs may help prevent these adverse events. Therefore, we conducted a prospective study to examine the diagnostic performance of a single pass with five TAFs in EUS-FNB. This single-center prospective observational study was conducted at a tertiary institution. From April 1, 2021, to August 31, 2022, 56 patients were enrolled. Three passes were performed using a 22-gauge Franseen needle (TopGain^R; Medicos Hirata, Tokyo, Japan) during the EUS-FNB. The number of TAFs were 5 in the first passes (5-TAF group) and 15 in the second and third passes (15-TAF group), respectively. Each TAF was performed with a suction technique using a 20-mL negative pressure syringe. The primary endpoint was the accuracy of the first pass, and the secondary endpoint was a qualitative comparison of the specimens between the 5-TAF and 15-TAF groups. All patients were followed up for more than 6 months. Qualitative evaluation was performed as follows: the adequate sample score ranged from 0 to 5, and the contamination and bloodiness scores ranged from 0 to 3.

Results

A total of 56 patients were enrolled in this study. Of them, data from 53 patients were analyzed. Three patients were excluded: two patients had an insufficient number of passes due to bleeding during the procedure, and one patient could not be punctured due to difficulty in identifying the lesion. The patient characteristics were as follows: median age, 73 years (range, 48–92 years), number of male patients, 28 (52.8%). The final diagnoses were malignant disease in 42 patients and benign disease in 11. The accuracy rate was 86.7% (95% confidence interval: CI, 74.7–94.5%) in the 5-TAF group, 81.1% (95% CI, 72.4–88.1%) in the 15-TAF group; the total accuracy rate in the 5-TAF and 15-TAF groups was 89.3%. There was no significant difference in the accuracy rate between 2 groups. The adequacy scores (average [standard deviation]) of the 5-TAF and 15-TAF groups were 4 [1.45] and 3.39 [1.81], respectively. The rates of adequacy scores ≥3 in the 5-TAF and 15-TAF groups were 84.9% and 72.6%, respectively (p=0.09). The contamination scores of the 5-TAF and 15-TAF groups were 1.57 [1.01] and 1.91 [1.06], respectively. The rates of contamination scores ≤1 in the 5-TAF and 15-TAF groups were 51.9% and 34.6%, respectively (p<0.05). The bloodiness scores of the 5-TAF and 15-TAF groups were 0.57 [0.64] and 0.86 [0.79], respectively. The rates of bloodiness score ≤1 in the 5-TAF and 15-TAF groups were 92.3%, and 75.0%, respectively (p<0.05). For each score, the 5-TAF group had a higher value than the 15-TAF group.

Conclusion

In the EUS-FNB with a Franseen needle, a single pass with five TAFs showed the possibility of obtaining a clinically acceptable accuracy rate and high-quality specimens.

References

1) Ishigaki K, Nakai Y, Oyama H et al. Endoscopic Ultrasound-Guided Tissue Acquisition by 22-Gauge Franseen and Standard Needles for Solid Pancreatic Lesions. Gut and Liver, 2020; 14(6): 817-825.
2) Li Z, Liu W, Xu X et al. A Meta-Analysis Comparing Endoscopic Ultrasound-guided Fine-needle Aspiration With Endoscopic Ultrasound-guided Fine-needle Biopsy. J Clin Gastroenterol 2022; 56(8): 668-678.
3) Mizuide M, Ryozawa S, Fujita A, et al. Complications of endoscopic ultrasound-guided fine needle aspiration: a narrative review. Diagnostics (Basel). 2020; 10: 964.

Disclosure

The authors have no conflicts of interest directly relevant to the content of this article.