Introduction

Mast cells are the primary cells that cause acute and chronic colitis due to irradiation causing radiation-induced colitis (RIC). Herein, we investigated whether pre-treatment with tranilast, mast cell inhibitor, could alleviate RIC.

Aims & Methods

A total of 23 Sprague Dawley (SD) rats were randomly divided into three groups control (n=5, C), irradiation group (n=9, RG), and tranilast pre-treated irradiation group (n=9, TG). Tranilast (100 mg/kg) was administered with meal for 10 d to TG, then Gamma ray (20 gray single dose) was irradiated to the pelvis of RG and TG. Ten weeks after irradiation, the rats were euthanized. Rectal tissue samples were stained and the total inflammation score (TIS) and mast cell count were assessed histopathologically. Expression of MUC2, MUC5AC and matrix metalloproteinase (MMP)-9 were also assessed immunohistochemically

Results

Either TIS or some components of TIS including epithelial atypia, vascular sclerosis and colitis cystica profunda, were significantly higher in RG than in TG (p=0.02, 0.038, 0.025, 0.01, respectively). The median number of infiltrating mast cells was significantly higher in the RG (27.5±18.40)) than in TG (6.0±6.02) (P=0.034). Quantitatively, the number of MMP-9-positive cells was significantly higher in the RG (23.67±19.00) than in the TG (10.25±8.45) (p<0.05).

Conclusion

TIS and MMP9 exhibited strong associations (correlation coefficient r=0.6, p<0.05) Immunohistochemically, mucin-lake of CCP showed MUC2 positivity only but was negative for MUC5AC. Conclusively, tranilast pretreatment in RIC shows an anti-inflammatory effect on the RIC with reducing mast cell infiltration and MMP expression

Introduction

Chronic fatigue is a debilitating symptom and has major impacts on the quality of life of patients with chronic inflammatory conditions. In IBD, an estimated 50% of patients suffer from persistent fatigue despite successful treatment of intestinal inflammation. During active disease flares, this number jumps to 80% (Borren et al. 2018). Tryptophan metabolites are not only associated with disease activity in UC and CD, but also with chronic fatigue (Kavyani et al. 2022). Thus, our aims are (1) to characterize the relationship between fatigue and tryptophan derivatives and (2) to understand the metabolic dynamics arising when fatigue symptoms improve following therapeutic intervention.

Aims & Methods

In a prospective open label cohort of patients with moderate-to-severe Crohn’s disease (CD, n = 71) and ulcerative colitis (UC, n = 94) assigned to biologics therapy or JAK inhibitors, fatigue was assessed by the fatigue subscale of the Functional Assessment of the Chronic Illness Therapy – Fatigue (FACIT-F) questionnaire at therapy induction and 2 and 14 weeks thereafter. A FACIT-F score of <30.1 was considered severe fatigue while a score of >40 was considered no relevant fatigue. Clinical response at week 14 was defined as Crohn’s Disease Activity Index (CDAI) <150 and reduction of Partial Mayo Clinical Score (PMCS) >50% vs. baseline, respectively. We used targeted mass spectrometry to quantify the levels of 13 tryptophan derivatives and neopterin in a subset of patient serum in the weeks following therapy induction (at 0, 2, and 14 weeks, n = 120 individuals).

Results

Half of the recruited patients had severe fatigue at baseline (50.3%). Of the 120 patients who reached week 14 and had FACIT-F scores available, severe fatigue was experienced by 45.9% of the patients who did not respond to therapy and the rate was reduced to 13.2% in therapy responders. We found 8 metabolites positively associated with FACIT-F: tryptophan, kynurenic acid, kynurenine, picolinic acid, xanthurenic acid, serotonin, indole-3-proprionic acid, and quinaldic acid, while neopterin was negatively associated (FDR < 0.05). Four of these metabolites changed dynamically as a function of the extent of fatigue improvement: tryptophan, kynurenine, xanthurenic acid, and serotonin (FDR < 0.05). In all cases, the rate of change of these metabolites increased as a function of fatigue improvement.

Conclusion

Fatigue is linked to a diverse array of tryptophan metabolites. Notably, all of the significantly associated tryptophan derivatives were positively associated with FACIT-F, meaning that as fatigue symptoms improve, tryptophan metabolite levels increase. Many of these metabolites have previously been linked to symptom severity in IBD: for example, tryptophan, kynurenic acid and xanthurenic acid all tend to increase with symptom alleviation (Nikolaus et al. 2017, Michaudel et al. 2022). While the kynurenine-to-tryptophan ratio is elevated in active IBD (Nikolaus et al. 2017), this ratio did not convey a specific, fatigue-related signature. Considering that some patients continue to suffer from persistent fatigue even during disease quiescence, further work is needed to disentangle the impact of tryptophan metabolism on therapy response from its role on fatigue improvement.

Disclosure

F. Tran receives scientific funding from Sanofi, received consulting fee's from LEK Consulting and speaker's fees from Lilly, Janssen, Falk, Abbvie, Celltrion, onkowissen.de, CED Service GmbH. S. Schreiber reports consulting fees from Abbvie, Arena, BMS, Biogen, Celltrion, Celgene, IMAB, Gilead, MSD, Mylan, Pfizer, Fresenius, Janssen, Takeda, Theravance, Prevention Bio, Protagonist and Falk.

Introduction

Percutaneous transesophageal gastrotubing (PTEG) was established as an alternative route to access the gastrointestinal tract for the patients that Percutaneous Endoscopic Gastrostomy was contraindicated. PTEG will be an ideal method of tube feeding for the patients without indication of PEG.

Aims & Methods

The aim of this study is to evaluate the clinical usefulness of PTEG for the patients who need tube feeding. A rupture-free balloon (RFB) catheter is inserted into the upper esophagus. Percutaneous balloon puncture with a specialized needle is then performed from the left side of patient’s neck under ultrasonographic control. A guide wire is inserted through the needle into the RFB, followed by a dilator and sheath. A placement tube is then inserted through the sheath, and the sheath is removed. Double Balloons equipped Over tube type RFB were used instead of primary RFB in thirty-five cases that the puncture needle is punctured into the over tube trough the balloon. We perform PTEG in a total of 115 patients (78 men and 37 women, mean age 77.7 years) in whom PEG was not feasible for nutrition. Sixty-one patients had prior gastrectomy , 30 patients had gastric herniation into the thoracic cavity , 6 patients had there stomach located behind the colon , 4 patients had ventriculo-peritoneal shunt tube in front of the stomach and 4 patients had peritoneal carcinoma.

Results

Satisfactory results were achieved in all 115 patients. Median follow-up was 322.0 days. There were no patients who needed a nasogastric tube after PTEG. Seven of 115 patients were able to free from tube feeding due to PTEG tube feeding support. About the complications, there was 1 patient with severe bleeding requiring blood transfusion, one patient had tracheal penetration, which was managed conservatively. Other complications were minor oozing bleeding in seven patients that did not require blood transfusion, subcutaneous emphysema in two patients, which were managed conservatively. Complication rate was 10.4%. No patient required surgical treatment or died after PTEG.

Conclusion

PTEG is feasible, safe, and useful　for long-term nutrition for the patient who is contraindicated to PEG. PTEG may become the only procedure of the liberation from nasogastric tube for the patient who is contraindicated to PEG PTEG is the ideal solution for the patients with PEG contraindicated in the tube feeding.

Disclosure

Nothing to disclose

Introduction

Irritable bowel syndrome (IBS) is a bothersome condition with long term pain and bowel symptoms and the most common cause of referral to gastroenterologists in the United Kingdom. Despite this, IBS is poorly understood as a clinical entity. Furthermore, IBS has numerous comorbidities but the full spectrum of these and how they relate to IBS has not been studied.

Aims & Methods

Using clustering analysis on the UK Biobank dataset, an adult cohort (age > 40 years), we aimed to define the top co-morbidities associated with IBS and develop a machine learning model to predict IBS. Co-morbidities in patients based on ICD-10 Summary Diagnosis codes 2 years prior to and 2 years following diagnosis with IBS were assessed and clusters defined. These were compared with a control group of non-IBS patients. Several machine learning algorithms (K-Means, Linear Discriminant Analysis, Gaussian Mixture Models) were compared for accuracy.

Results

Amongst 18000 total adults (aged over 40), 8168 patients coded for IBS, 75% of whom were female. The top ten comorbidities (Table 1) found in IBS patients included diverticular disease, hypertension, hernia, haemorrhoids, osteoarthritis, asthma, gastro-oesophageal reflux disease without oesophagitis, history of psychoactive substance abuse, hypercholesterolaemia, and cholelithiasis. K-Means achieved the highest accuracy (83%) for predicting IBS based on the co-morbidity profile.

Conclusion

Most clusters identified contained obesity, hypercholesterolemia, and hypertension, indicating a possible link with metabolic syndrome. Asthma and allergies suggest a possible cohort of IBS patients with atopy. Further research is needed to establish these links. In clinical practice, this could help both in predicting development of IBS, and also identify the cohorts of IBS on which certain therapies are more likely to work.

References

Drossman, D. A., Camilleri, M., Mayer, E. A., & Whitehead, W. E. (2002). AGA technical review on irritable bowel syndrome. Gastroenterology, 123(6), 2108-2131. doi:10.1053/gast.2002.37095
Snyder, N. (2023, 10 Feb 2023). Irritable bowel syndrome. BMJ Best Practice. Retrieved from https://bestpractice.bmj.com/topics/en-gb/122
Staller, K., Olén, O., Söderling, J., Roelstraete, B., Törnblom, H., Khalili, H., . . . Ludvigsson, J. F. (2021). Diagnostic yield of endoscopy in irritable bowel syndrome: A nationwide prevalence study 1987-2016. Eur J Intern Med, 94, 85-92. doi:10.1016/j.ejim.2021.08.001

Introduction

The degree of fibrosis during colorectal ESD varies and sometimes makes the procedure itself difficult. Preoperative prediction of fibrosis is expected to help develop a reliable strategy.

Aims & Methods

Of 1309 colorectal ESD lesions performed at our hospital between April 2012 and September 2022, 953 lesions larger than 20 mm were included after excluding post-treatment recurrence, SMT, and other conditions. Intraoperative fibrosis was classified into F0 (none), F1 (mild), and F2 (severe).

Results

Fibrosis was observed in 192 (20.1%) patients (F1; 143, F2; 49). The tumor diameter (median, range) was 23 (20-135), 30 (20-210), and 35 (20-115) mm in F0, F1, and F2 groups, respectively. The rate of the cecum (%) was 13.3 : 29.4 : 16.3, which was higher in F1. Overall, bleeding was observed in 17 patients (1.8%) and perforation in 3 patients (0.3%), and the frequency was similar in each group. The curative resection rate (%) was 98.4:91.6:59.2, with F2 being significantly inferior. The long treatment time (≥120 minutes) (%) was 1.7 : 9.1 : 46.9, showing a significant difference between F0 vs F1 and F1 vs F2, and the dissection speed (mean±SD, mm²/min) was 25.9±14.5 : 23.2±13.6 : 15.3±10.6, which was significantly slower in F2. The predictive factors of F1 and F2: straddling the folds, prior biopsy, lesion diameter, site, and morphology, were included in the study, and multivariate analysis showed that the predictive factors of F1 were straddling folds (OR;2.07,95%CI;1.39-3.11), lesion diameter ≥50mm (OR;4.68,95%CI;2.45-8.94), biopsy (OR;6.44,95%CI;3.32-12.5), NGPD (OR;4.31,95%CI;2.37-7.83), and cecum(OR;3.73,95%CI;2.35-5.92). The predictive factors of F2 were straddling folds (OR;2.34,95%CI;1.21-4.51), lesion diameter ≥50 mm (OR;7.29,95%CI;3.03-17.5), biopsy (OR;5.07,95%CI;1.81-14.1), and protruded type (OR;6.44,95%CI;3.23-12.8).

Conclusion

Colorectal ESD for fibrotic lesions was safe, but the curative resection rate was low in F2. F1-specific predictors were cecum and NGPD, and F2-specific predictors were protruded type, suggesting that the choice of surgeon and strategy should depend on the expected degree of fibrosis.

Introduction

Being two immune-mediated diseases (IMIDs), the association between multiple sclerosis (MS) and inflammatory bowel disease (IBD) is plausible, but data in the literature are conflicting.

Aims & Methods

The aim of our study was to evaluate the possible association between IBD and MS in a cohort of patients with IBD.

Results

In a retrospective study, we examined the medical records of 5,739 patients with a confirmed diagnosis of IBD followed in our clinic between 1978 and 2022.
Among these patients, we identified 14 with MS, with a prevalence of 0.24%. The reported prevalence of MS in general population in northern Italy in 2021 was 0.18% (P = 0.24). For each of the patients with MS identified, more than ten patients without MS were analyzed. The 14 MS cases were then compared with 342 controls. From the 14 MS patients, 12 (85.7%) were female and 2 (14.3%) were male, while in the control group, 158 (46.2%) were female and 184 (53.8%) were male (P = 0.004). As for therapy, significant differences were found on mesalazine (5 (41.7%) cases vs. 317 (92.7%) controls, P < 0.0001) and anti-TNF treatment (0% cases vs 26.6% controls, P = 0.03, respectively) at the time of MS diagnosis. Moreover, Kaplan-Meier curve analysis showed that the 20-year survival probability was 98.4% for patients with IBD, while for patients diagnosed with MS and IBD it was 82.1% (P = 0.02).

Conclusion

In conclusion, patients with IBD have a similar risk of developing MS compared to the general population, but female sex appears to increase the risk. Indeed, life expectancy at 20 years for patients with IBD and MS is lower than for patients with IBD alone.