Introduction

Many CD patients experience clinically „silent“ disease with active inflammation leading to complications and disability. Invasive and resource consuming procedures such as endoscopy, MR enterography and CT imaging have long been the mainstay of monitoring disease activity in CD. Intestinal ultrasound (IUS) is becoming an established non-invasive alternative for everyday point-of-care management of patients with CD. The most important ultrasound parameters associated with active CD include bowel wall thickness (BWT), bowel wall stratification (BWS), color-doppler signal (CDS) and the presence of mesenteric fat (i-fat). Several ultrasound scoring systems using some of these parameteres have been proposed in order to facilitate monitoring of CD patients as well as standardise reporting of intestinal ultrasound findings.

Aims & Methods

The study aim was to compare performance of IBUS-SAS (International Bowel Ultrasound Segmental Activity Score), BUSS (Bowel Ultrasound Score), Simple-US (Simple Ultrasound Score), and SUS-CD (Simple Ultrasound score for Crohn's disease) in detecting disease activity in CD patients. A single center retrospective analysis of stored IUS images and corresponding CD patient charts with endoscopy findings at the time of the ultrasound has been performed. Endoscopic activity was defined as SES-CD>3. After assessment of normal distribution using Kolmogorov-Smirnov and Shapiro-Wilk tests continuous variables were reported as median and interquartile ranges (IQR) or as mean ± standard deviation, whereas categorical variables were reported as frequencies with percentages. ROC curve analyses were conducted in order to determine AUCs and predictive cut-off value scores, with endoscopy serving as the reference standard. The Z statistic and Hanley & McNeil methodology were used to compare ROC curves. P values less than 0.05 were considered statistically significant.

Results

A total of 83 patients were included, 45.8% female with a mean age 41 years and median disease duration of 8 years. Endoscopic disease activity was present in 55 (66.3%) patients. Isolated ileal disease was present in 48.2%. Stricturing and penetrating disease phenotype was present in 41% and 39.8% of patients respectively. The results for ROC analyses, cut-off values for remission, sensitivity and specificity of four different IUS scores are shown in table 1. Statistically significant differences among scores haven't been observed.

Table 1. Comparison of intestinal ultrasound scores for detecting active Crohn's disease

Conclusion

All IUS scores performed well for detecting CD endoscopic activity which shows IUS can reduce the number of endoscopies in the CD patient population without sacrificing accuracy. We found no significant difference in the sensitivity and specificity of different scores in out patient cohort, hence clinicans can rely on the IUS score they are comfortable with using. Our cut-off values are in line with published data further confirming method robustness.

References

1. Dragoni G, Gottin M, Innocenti T, Lynch EN, Bagnoli S, Macrì G, Bonanomi AG, Orlandini B, Rogai F, Milani S, Galli A, Milla M, Biagini MR. "Correlation of ultrasound scores with endoscopic activity in Crohn's disease: a prospective exploratory study". J Crohns Colitis. 2023 Apr 6:jjad068. doi: 10.1093/ecco-jcc/jjad068.
2. Wang L, Xu C, Zhang Y, Jiang W, Ma J, Zhang H. External validation and comparison of simple ultrasound activity score and international bowel ultrasound segmental activity score for Crohn's disease. Scand J Gastroenterol. 2023 Feb 23:1-7. doi: 10.1080/00365521.2023.2181038. Epub ahead of print. PMID: 36825305.

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

Capsule endoscopy is the first-line examination for digestive bleeding with likely origin in the small bowel, in hemodynamically stable patients. In the 2022 update, ESGE guidelines recommend that, in the context of overt bleeding, capsule enteroscopy should be performed as soon as possible, ideally within the first 48 hours. In the previous guidelines, published in 2015, the recommended window was 14 days.

Aims & Methods

This study aimed to evaluate the improvement in yield offered by the new recommendations regarding the timing of urgent capsule enteroscopy. Patients with suspected overt middle gastrointestinal bleeding between January 2005 and November 2022 were retrospectively analyzed. Diagnostic and therapeutic yield, rebleeding rate, and mortality were compared when capsule enteroscopy was performed within the first 48 hours, within the first 14 days, or between the 3rd and 14th day after admission.

Results

A total of 138 patients were included (58.7% men, median age 66 years), 87 of whom (63.0%) underwent capsule enteroscopy within the first 48 hours after hospital admission. The median follow-up was 55 months (5-180). The diagnostic yield (presence of blood or lesions with bleeding potential) was slightly higher when capsule enteroscopy was performed within the first 48 hours (81.6% versus 76.5%, p=0.349). On the other hand, capsule enteroscopy within the first 48 hours was significantly associated with higher therapeutic yield (endoscopic, radiologic, or surgical treatment) - 54.0% versus 39.2%, p=0.02. The rebleeding rate was significantly lower in patients undergoing enteroscopy within 48 hours after admission (19.5% versus 29.4%, p=0.04). On the other hand, overall mortality at 36 months did not differ between strategies (21.8% and 25.5%, p=0.401).

Conclusion

Performing capsule endoscopy within the first 48 hours, as recommended by recently published guidelines, is associated with favourable short- and long-term clinical outcomes.

Introduction

Esophageal dysphagia is a common complaint in daily clinical practice. After excluding structural and motility disorders, it may be related to functional disorders, which are challenging to diagnose and manage, leading to high health care utilization and both patient and physician dissatisfaction.

Aims & Methods

This is a prospective multicentric 6-months follow-up study to characterize dysphagic patients with normal esophageal motility, in terms of epidemiology and clinical aspects, focusing on patient-reported outcome measures, and evaluate their evolution at 6-months.

Results

From 2021-2024, 91 patients were recruited, 78.0% female, with a median age of 65 years [22-88]. Of these, 27.5% (n = 25) suffered from rheumatologic or endocrinologic disorders, and 56.0% were previously exposed to medical therapies.
Dysphagic symptoms had a median duration of 3 years [1-31], with a median Eckardt of 3 [0-9], PROMIS GI Disrupted Swallowing (PDS) of 60.4 [40.3-84.1], EuroQol-5D TTO of 0.592 [-0.055-1] and VAS of 70 [0-100].
Compared to non-dysphagic participants (n=123), these patients had significantly worse Eckardt, EuroQol-5D and PDS scores (p-values <0.001).
Compared to esophageal motility disorders (Chicago V4.0), the Eckardt and PDS scores in this group were significantly lower when compared to EGJ outflow disorders (p-value <0.001 and 0.003), without differences regarding EuroQol-5D.
Regarding gastroesophageal reflux, 24 (26.4%) patients had a positive GERD-Q questionnaire and 3 had an objective GERD diagnosis. Even though, compared to motility disorders, this score was significantly lower in this group when compared to EGJ outflow disorders (p-value 0.001).
Medical treatments (PPI, amitriptyline) were optimized in 6 patients (6.6%), without any differences in Eckardt or EuroQol-5D scores at 6-months. However, at 6-months, the PDS improved in untreated patients (p-value <0.001).

Conclusion

Non-obstructive dysphagia with normal esophageal motility has a negative impact on quality of life. However, symptoms tend to have a favorable course independently of treatment, therefore mandating a holistic management.

Introduction

Sporadic neoplasias (SNs) and ulcerative colitis-associated neoplasias (UCANs) can occur in patients with UC. Differences in the characteristics and prognoses between UCANs in patients with UC and SNs in patients without UC have been assessed in numerous previous studies. However, only a few studies have focused on the characteristics and prognoses of SNs in patients with UC. It is important to distinguish between UCANs and SNs, because they have different prognoses and therefore need different treatment strategies.

Aims & Methods

This study aimed to evaluate the clinical features and prognoses of SNs detected in patients with UC, both within and outside the affected area. A total of 141 SNs in 59 patients with UC, which were detected by surveillance colonoscopy (SCS) at Hiroshima University Hospital between January 1999 and December 2021, were included. In our hospital, we perform SCS for UC patients with left-sided or total colitis and with a disease duration of more than 7 years, if possible, in the remission stage. SNs were diagnosed based on their location, endoscopic features, and histopathological findings. The final diagnosis was made by histopathological evaluation of the excised specimens and confirmed by more than one gastrointestinal pathologist. The histopathological diagnosis of SN was made according to the pathological features described in the recent European Crohn's and Colitis Organization and the European Society of Pathology statement on histopathology. Immunohistochemical evaluation of Ki67 and p53 was performed in all cases. SNs, especially sporadic adenomas, have regular neoplastic glands with low amounts of stroma, and rarely have a mixture of benign/dysplastic crypts. Although UCANs sometimes have a surrounding flat area with overexpression of p53, SNs have no such area and have a distinct border between the neoplastic glands and non-neoplastic mucosa. SNs have Ki67 expression mainly in the superficial zone and have low levels of p53 expression.

Results

The mean age at first SN detection was 58.8 years, and the mean duration of UC was 9.9 years. Male patients represented 64.4% of the enrolled patients. The most common type of UC was the total colitis type (47.5%). With regard to their clinical course, approximately half of the patients (49.2%) presented with the relapse-remitting type. Among the 141 SNs, 129 lesions (91.5%) were diagnosed as adenomas, five (3.5%) as Tis carcinomas, two (1.5%) as T1a carcinomas (superficially submucosal invasive carcinoma: <1,000 µm), and five (3.5%) as T1b carcinomas (deeply submucosal invasive carcinoma: ≥1,000 µm). There were 86 (61.0 %) SNs in the right colon, 44 (31.2%) in the left colon, and 11 (7.8%) in the rectum. When classified as outside or within the affected area of UC, 100 (70.9%) SNs occurred outside and 41 (29.1%) within. Most SNs (135 lesions, 95.7%) underwent endoscopic resection, and only six lesions (4.3%) underwent surgical resection. Among the 59 patients included in this study, synchronous SNs occurred in 14 (23.7%), and metachronous multiple SNs occurred in 24 (40.7%) patients. The 5-year cumulative incidence of metachronous multiple SNs was higher in patients with synchronous multiple SNs (54.2%) than in those without (46.4%). The histology, size, and background mucosa of the initial SNs were not associated with the incidence of metachronous SNs in our study.

Conclusion

UC patients with synchronous multiple SNs were at higher risk of developing metachronous multiple SNs and may require close follow-up compared to patients without synchronous SNs.

Introduction

Double-headed capsules enable the non-invasive one-step endoscopic evaluation of both the small bowel and colon (pan-intestinal capsule endoscopy, PCE).

Aims & Methods

We aim to evaluate the diagnostic accuracy and safety of PCE vs. the current standard of care (conventional colonoscopy) as the first-line examination in patients with iron deficiency anaemia (IDA) and/or overt bleeding after a non-diagnostic upper endoscopy (suspected mid or lower gastrointestinal bleeding, MLGIB).
We conducted a prospective, single-centre, single-blinded cohort study including consecutive patients with suspected MLGIB. All patients were submitted to PCE, followed by same-day colonoscopy under deep sedation. The physicians performing PCE and conventional colonoscopies were independent and blinded to each other’s observations. The diagnostic yield for potentially haemorrhagic lesions (PHL) was compared for efficacy analysis, and adverse events were assessed for both examinations. The gold standard diagnosis was defined by consensus panel. This trial has been registered in ClinicalTrials.gov (ID NCT04782986).

Results

We included 100 consecutive patients with suspected MLGIB, mean age 66.5 (18-92) years, 65% female gender, presenting with IDA (81%) or overt bleeding (19%). Mean haemoglobin level was 8.4 (4.1-12.8) g/dL and 40% were inpatients. For PCE, the PillCam Crohn’s® capsule was used in 88 patients, and PillCam COLON® 2 in the remaining. Patients with overt bleeding performed PCE within 2 weeks in 70% of cases, 15% in the first 72h after the bleeding episode. PCE was complete in 76% of cases, vs. colonoscopy 95% (p<0.01). The quality of bowel preparation was adequate in 72% of PCE vs. 85% of colonoscopies (p=0.012). Overall, PHL were diagnosed, based on the combination of PCE + colonoscopy, in 46% of patients, corresponding to small bowel and/or colon angioectasias in more than two-thirds (69.6%) of cases. PHL were detected by both examinations in 13/46 (28.3%), only by colonoscopy in 3/46 (6.5%), and only by PCE in 30/46 (65.2%) of cases (p<0.01). Overall, colonoscopy detected PHL in 23% of the entire cohort, which means 50% (23/46) of all patients with PHL according to the consensus panel, while for PCE the overall diagnostic yield was 44%, meaning 95.7% (44/46) of all PHL (p<0.01). Considering the gold standard diagnosis for PHL, colonoscopy had a sensitivity of 23/46=50%, specificity 54/54=100%, positive predictive value (PPV) 23/23=100% and negative predictive value (NPV) 54/77=70,1%, while for PCE the sensitivity was 44/46=95.7%, specificity 54/54=100%, PPV 44/44=100% and NPV 54/56=96.4%. Thirty-one percent of patients had PHL accessible to ileocolonoscopy; in those cases, the PCE was able to make the diagnosis in 29/31 (93.5%) vs. conventional colonoscopy in 23/31 (74.2%) of cases, p<0.01. Regarding safety, no significant adverse events occurred with PCE, vs. 2% (cardiopulmonary) with conventional colonoscopy.

Conclusion

PCE is safe and more effective than conventional colonoscopy in identifying PHL both in the small bowel and the colon, and could be considered as a first-line examination in patients with IDA or overt bleeding after a non-diagnostic upper endoscopy. In more than half of patients with suspected MLGIB, PCE does not detect any PHL either in the small bowel or the colon, dismissing any further invasive endoscopic investigations.

Disclosure

Medtronic provided financial support to the acquisition of some of the capsules which were used in the trial