Introduction

The role of the GUT microbiota in modulating local and systemic immune responses has triggered scientific interest in its influence on anticancer immune reaction and immunotherapy outcomes. Immune checkpoint inhibitors (ICI) have clinically relevant efficacy only in 3% to 6% of metastatic CRC (mCRC) patients. In this regard, in a single-arm, phase II trial, Cetuximab-AVElumab mCRC (CAVE-mCRC), the combination of cetuximab plus avelumab was evaluated as a rechallenge strategy in chemo-refractory RAS wild type (WT) mCRC patients, demonstrating the efficacy and high tolerability of this therapeutic combination.

Aims & Methods

Through an exploratory analysis of basal pre-treatment fecal microbiota species in patients from the CAVE-mCRC trial, we aimed to identify gut bacteria correlating with the antitumor activity of avelumab plus cetuximab. For this purpose, on fecal samples collected at baseline before treatment, sequencing of the V4 region of the bacterial 16S rRNA gene was performed; moreover, real-time PCR was used to detect the presence of hydrogen consumers and butyrate producers. Hence, to further evaluate and validate the results, we extended this analysis to a subgroup of patients from the CAVE-Lung trial.

Results

16S rRNA sequencing revealed 23027 bacteria species in basal fecal samples of 14 patients from the CAVE-mCRC trial. Among the 10 more represented bacteria species, the linear regression analysis revealed two butyrate-producing bacteria, Aghatobacter M104/1 and Blautia SR1/5, significantly associated with better progression-free survival (PFS). In five long-term responding patients (PFS: 9-24 months) significant increases of Agathobacter M104/1 (p=0.018) and Blautia SR1/5 (p=0.023) were found compared to nine patients with shorter PFS (2-6 months). For Agathobacter M104/1, median PFS (mPFS) was 13.5 months (95% confidence interval [CI], 6.5-20.5 months) vs 4.6 months (95% CI, 1.8-7.4 months) (p= 0.006). For Blautia SR1/5, mPFS was 5.9 months (95% CI, 2.2-9.7 months) vs 3.6 months (95% CI, 3.3-4.0 months) (p=0.021). The binomial logistic regression revealed a statistically significant association between the PFS and C-reactive protein (CRP) levels (OR: 1.84, 95% CI: 1.78-1.92, P= .010), the presence of Agathobacter M104/1 (OR: 1.98, 95% CI: 1.78-2.10, p=0.041) and Blautia SR1/5 (OR: 2.52, 95% CI: 2.40-2.61, p< 0.0001) (table 1). Similarly, in the CAVE-Lung validation cohort, Agathobacter M104/1 and Blautia SR1/5 expression was associated with PFS according to their presence or absence in basal fecal samples.

Table 1. Binomial logistic regression of variables influencing PFS

Conclusion

For the first time, we demonstrated that two butyrate-producing bacteria could become potential biomarkers for cetuximab plus avelumab antitumor activity in chemorefractory colorectal cancer and non-small cell lung cancer patients.

References

1. Alexander JL, Wilson ID, Teare J, Marchesi JR, Nicholson JK, Kinross JM. Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat Rev Gastroenterol Hepatol. 2017
2. Wang D, Zhang H, Xiang T, Wang G. Clinical Application of Adaptive Immune Therapy in MSS Colorectal Cancer Patients. Front Immunol. 2021
3. Martinelli E, Martini G, Famiglietti V, et al. Cetuximab rechallenge plus avelumab in pretreated patients with RAS wild-type metastatic colorectal cancer: the phase 2 single-arm clinical CAVE trial. JAMA Oncol. 2021; 7:1529

Introduction

The extent of gastric atrophy(GA) is closely related to the incidence of Intestinal-type gastric cancer (GC). According to the Kimura-Takemoto classification, determining whether the atrophy extends beyond the cardia is key to assess the extent of GA. However, there is significant difficulty in determining whether the cardia is atrophied under endoscopy.

Aims & Methods

This study developed a novel artificial intelligence (AI)-assisted white light endoscopy system for identifying the cardia part and diagnosing cardia atrophy . In this multicenter study, patients undergoing upper gastrointestinal endoscopy at 5 hospitals in China were prospectively included between November 2022 and December 2024. Among them, a total of 895 patients from 2 units were assigned to the training and validation sets (292 with cardia atrophy and 603 without cardia atrophy) to establish a cardia atrophy diagnostic model. 220 patients from our unit (84 with cardia atrophy and 136 without cardia atrophy) were included in the internal test set. Additionally, a total of 354 patients from 3 other units were included in the external test set (106 with cardia atrophy and 248 without cardia atrophy). In the internal and external test sets, 3 senior and 3 junior endoscopists made online diagnoses, comparing the performance differences between physicians with different levles of experience and the AI-assisted cardia atrophy detection system.

Results

This study established a AI-assisted cardia atrophy diagnostic model and tested its diagnostic performance with multicenter image data in internal and external tests. In the internal test dataset, the accuracy, sensitivity, and specificity of the AI-assisted system were 0.927, 0.941, and 0.919, respectively, with a PPV of 0.878, NPV of 0.962, and AUC of 0.967. In the external test dataset, the accuracy, sensitivity, and specificity were 0.918, 0.894, and 0.931 respectively, with a PPV of 0.874, NPV of 0.943, and AUC of 0.953. Further comparison of the diagnostic efficiency of the AI-assisted system with endoscopists of different levels of experience revealed that both in the internal and external test set, the diagnosis accuracy, sensitivity, specificity, PPV, and NPV of the AI-assisted system were all higher than those of senior endoscopists. TheAI-assisted cardia atrophy diagnostic ROC curve area (AUC) was 0.967 and 0.953 in the internal and external test sets, respectively. Heat map analysis further showed a high consistency between theAI-assisted system and endoscopists in cardia atrophy diagnosis.

Conclusion

Our newly developed AI-assisted cardia atrophy diagnostic system shows superior performance in identifying cardia atrophy compared to senior endoscopists, and can be used to guide white light endoscopic judgment and targeted biopsies for cardia atrophy.

Introduction

Adenoma detection rate (ADR) has been inversely associated with the risk of interval colorectal cancer. According to a recent positional statement of the European Society of Gastrointestinal Endoscopy (ESGE), Artificial Intelligence is expected to increase ADR.

Aims & Methods

The aim of the study is to evaluate the benefit of a computer-aided detection device (CADe Endo-AID) in a consecutive, non-selected series of patients undergoing colonoscopy. This is an interim analysis of an Italian prospective multicenter randomized control trial (RCT) that included patients aged 40-85 scheduled for screening, surveillance or diagnostic colonoscopy randomly assigned to CADe (Endo-AID, Olympus, Japan) or standard colonoscopy (SC). Patients with a Boston Bowel Preparation Scale (BBPS) < 2 in any segment were excluded from the analysis. Polyp Detection Rate (PDR), Polyp Per Colonoscopy (PPC), ADR, Adenoma Per Colonoscopy (APC), Serrated Detection Rate (SDR), Advanced adenoma (villous histology and/or high-grade dysplasia and/or diameter ≥ 1 cm) and the presence of ≥ 3 precancerous lesions were evaluated in the two groups.

Results

901 patients were enrolled of whom 62 were excluded for inadequate bowel cleansing. Therefore, 839 subjects (428 CADe vs 411 SC) were included in the final analysis. ADR was significantly higher in CADe than in the control group [50.2% (215/428) vs 41.6% (171/411) p= 0.01]. CADe also significantly increased PDR, PPC, and APC [67.5% (289/428) vs 55.5% (228/411) p< 0.01; 1.68 vs 1.34 p< 0.01; 1.17 vs 0.86 p< 0.01, respectively]. SDR, advanced adenomas, and ≥ 3 precancerous lesions were higher in the intervention group without reaching statistical significance. Endpoints were evaluated in a subgroup analysis for BBPS scores (116 CADe/115 SC patients with BBPS 6 and 266 CADe/244 SC patients with BBPS 9). Results are summarized in Table 1.

Conclusion

The preliminary results of the present RCT show an increase in the diagnostic yield of AI-assisted colonoscopy in all the calculated indicators in a non-selected population undergoing colonoscopy.

Introduction

Intestinal ultrasound (IUS) has proven to be a valuable tool for accurately detecting intestinal damage and characterizing disease behavior in Crohn’s disease (CD). IUS scoring systems for CD activity have been developed, however all the studies had methodological flaws. Therefore, studies comparing and validating the existing IUS scores in CD patients are required.

Aims & Methods

In this study, we aimed to compare two main existing scores, Bowel Ultrasound Score (BUSS) and International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) in patients with ileal CD using the simplified endoscopic activity score for CD (SES-CD).
An observational cross-sectional study was performed to evaluate the disease activity in adult CD patients with ileal involvement between November 2019 and February 2024. All patients had undergone ileocolonoscopy and IUS, the time interval between the two procedures was lower than 10 days. Receiver operating characteristic (ROC) curve analyses was performed for BUSS and IBUS-SAS to predict SES-CD ≤2 for CD.

Results

Total 56 adult patients with ileal CD were included in the study, 38 patients (67.9%) were male, the median age was 40.5 (IQR 26-46.75) years and the median duration of the disease was 8.4 (IQR, 4.93-10.29) years. In the endoscopically remission (SES-CD ≤2) group; the median BUSS was 2.63 (IQR 2.12-3.45) and the median IBUS-SAS was 14 (IQR, 11.3-18.4), while in the endoscopically active (SES-CD >2) group; the median BUSS was 5.67 (IQR, 3.47-7.76) and the median IBUS-SAS was 49.7 (IQR, 23.3-72.65). The median BUSS and median IBUS-SAS in the endoscopically remission group were significantly lower than those of the endoscopically active group (p< 0.001, for both). The cut-off value for BUSS to determine endoscopic remission (SES-CD ≤2) was 3.9 (AUC: 0.839, 95% CI: 0.737-0.941, sensitivity: 92%, specificity: 73%, p < 0.001), while the cut-off value for IBUS-SAS to establish endoscopic remission (SES-CD ≤2) was 24.4 (AUC: 0.871, 95% CI: 0.780-0.962, sensitivity: 100%, specificity: 73%, p < 0.001).
There was a very high positive correlation between BUSS and IBUS-SAS (r=0.914, p<0.001), a high positive correlation between BUSS and SES-CD (r=0.659, p<0.001), a moderate positive correlation between BUSS and CRP (r=0.577, p<0.001). There was a high positive correlation between IBUS-SAS and SES-CD as well as IBUS-SAS and CRP (r=0.728, p<0.001 and r=0.657, p<0.001 respectively).

Conclusion

In this study, we found that the most accurate cut-off value for BUSS was 3.9 and the most accurate cut-off value for IBUS-SAS was 24.4 in CD patients with endoscopic remission (SES-CD ≤2) group. Also, we have confirmed that both BUSS and IBUS-SAS significantly correlate with endoscopic activity in a real-world cohort.

Introduction

A novel device intended to evaluate motility in patients at risk for dysmotility and enteral feeding intolerance was developed. This VIPUN Gastric Monitoring System (GMS) consists of a feeding tube with a balloon attached to its distal end and a control unit. Once the balloon is positioned in the stomach the control unit can inflate the balloon, record intra-balloon pressure and analyze gastric motility.

Aims & Methods

Our aim was to validate the GMS as a gastric motility monitoring system by comparing its performance to the gold standard, high-resolution manometry. The primary hypothesis was that the contraction durations recorded by the GMS and manometry are strongly correlated (ρ > 0.70). Secondary objectives: To correlate the contraction frequency observed by expert gastroenterologists and by GMS analysis software on GMS and manometry, and to observe gastric accommodation upon nutrient intake.
In this monocentric, single-arm, interventional study, a GMS prototype (VIPUN Medical, Belgium) was tested in healthy adults. A solid state manometry catheter (UniTip, Unisensor AG, Switzerland) was used as comparator. The balloon catheter was inserted through the nose. The manometry catheter was inserted through the other nare and positioned with the tip in the duodenum, as verified using fluoroscopy. Afterwards, the GMS catheter balloon was inflated with 120 mL air. The participant was placed in semi-recumbent position for the 2.5 h pressure measurement. After 2 h, a liquid meal (400 kcal, 1.5 kcal/mL) was infused via the GMS catheter.
For manometry, only the channels that were consistently in the stomach were analyzed. Duration of contractility (primary outcome) was calculated as the time baseline-corrected pressure waves exceeded a subject- and technology-specific pressure threshold (1). The identification of individual gastric contractions (secondary outcome) was done by two independent readers, a third reader served as adjudicator. Additionally, GMS software was used for the detection of individual gastric contractions. Results are shown as mean (standard deviation).

Results

13 healthy volunteers (6 women, 27.5 (8.1) years) were included. GMS catheter placement was feasible and safe. Intragastric balloon inflation was well-tolerated. No serious or unanticipated adverse events occurred.
For the primary outcome, the Spearman correlation between the contraction duration recorded by GMS and manometry was 0.96 (p < 0.01). The sum of contractile activity per subject was similar: 2588.7 (1872.2) and 2722.3 (1768.7) seconds on manometry and GMS, respectively (p = 0.44, paired t-test, see Table 1).
For the number of contractions identified visually by readers, the correlation between GMS and manometry was 0.71 (p < 0.01) . Using GMS software for detection of individual contractions on GMS, the correlation with reader-identified contractions on manometry was 0.87 (p < 0.01).
Nutrient infusion resulted in a significant decrease in tonic (-1.7 (0.96) mmHg) and phasic (-3.4 (3.1) contractions/10 min) contractility.

Conclusion

The observed strong correlations with the gold standard, manometry, validate the performance of the VIPUN GMS as a gastric monitoring system.

References

1. Janssen P, Goelen N, Tack J. A comparison of various intragastric balloons for the assessment of gastric motility. Neurogastroenterol Motil. 2018;30(12):e13453.

Introduction

The BELCOMID study recruited immune mediated inflammatory disease (IMID) patients during the COVID19 pandemic. Patients were evaluated before vaccination, after onset of the vaccination campaign and after onset of booster vaccinations. Clinical data, Nucleocapsid(N-)antibodies and Spike(S-)antibodies were assessed.

Aims & Methods

Current subgroup analysis aimed to firstly, explore factors associated with N-/S-antibody response in IMID patients with different COVID19 vaccination status. Five patient groups were identified. G1: no vaccination before the vaccination campaign, G2: complete baseline vaccination, G3: 1 booster, G4: 2 boosters, G5: patients refusing every vaccine even after the booster campaign. We report on influence of IMID treatment and smoking status.
Secondly, we explored influence of SARS-CoV2 infection and vaccination on IMID flare-up.

Results

Demographics of 2165 recruited IMID patients are shown in Table.
After baseline vaccination (G2) odds of N-seroconversion were higher in patients treated with combined IMM/TIMT (OR2.52, p=0.023). No other association with N-seroconversion was found.
Mean S-antibody titre increased progressively from G2 to G4. After completed baseline vaccination (G2), odds of S-antibody seroconversion were lower in those treated with TIMT (OR0.28, p=0.0079) particularly rituximab (OR0.0354, p<0.001), IMM (OR0.276, p<0.001), combined IMM/TIMT (OR0.156, p<0.001) and systemic steroids (OR0.183, p<0.001). IMID flare prior to vaccination was associated with lower risk of S-seroconversion (RR0.94, p<0.001). By contrast, mean S-titre was higher for those treated with antiIL23 (mean ratio 2.17, p=0.011) and vedolizumab (mean ratio 1.84, p<0.001) in G2.
After 1 booster (G3), lower odds of S-seroconversion remained with rituximab (OR0.0368, p<0.001), IMM (OR0.222, p=0.0014), combined IMM/TIMT (OR0.15, p<0.001) or systemic steroids (OR0.0637, p<0.001). Vedolizumab was associated with lower odds of being in the lowest S-titer quartile (OR0.206, p<0.001). Odds for S-antibody seroconversion with anti-TNF were higher compared to rituximab both for patients in G2 (OR26.3, p<0.001) and G3 (OR27.5, p<0.001).
Patients who received 2 boosters (G4) all had S-seroconversion and no IMID treatment modality was associated with higher odds of being in the lowest quartile.
After baseline vaccination (G2) smokers had higher risk of being in the lowest S-antibody titer quartile (RR1.45, p=0.0098). This observation persisted after 1 booster (G3)(RR1.42, p=0.0122) but was no longer noticed after 2 boosters (G4).
After start of booster vaccinations, 25.17% of patients had experienced IMID flare-up in the previous months. No significant association between IMID flare-up rate and previous SARS-CoV2 infection was found. There was no increased risk of IMID flare-up with additional booster vaccination. However, patients who received 2 booster vaccines showed a lower RR for IMID flare-up compared to those who only received 1 booster (RR0.70, p=0.0067).

Conclusion

Certain immune-modulating treatment modalities and smoking may blunt serologic COVID19 vaccination responses. However, this is overcome by repeated booster vaccination without increased risk of IMID flare-up.

Disclosure

The BELCOMID study group received research grants from following pharmaceutical companies: Almirall, Roche, Janssen, Pfizer, Eli Lilly, Amgen, Biogen, Mylan, LEO Pharma. These companies had no role in study design, conduct nor reporting of results.

Introduction

Computed tomography colonography (CTC) has been developed as a less invasive alternative method to colonoscopy for colorectal cancer screening. Some subjects who underwent CTC reported abdominal pain induced by carbon dioxide gas injection during examination. We speculated that pain perception during CTC might reflect visceral hypersensitivity related to irritable bowel syndrome (IBS).

Aims & Methods

In this study, we investigated whether pain perception induced by carbon dioxide gas injection during CTC is different between patients with IBS and healthy controls. Furthermore, we evaluated the correlation between the pain score during CTC and the severity of the IBS symptom or the quality of life of patients with IBS. A prospective study of consecutively registered patients who underwent CTC for colorectal cancer screening in a single medical center was conducted. IBS was diagnosed using the Rome IV criteria, and patients with IBS were classified into IBS subgroups according to the predominant stool pattern experienced by the patient. In addition, all subjects completed the IBS Severity Scale (IBS-SS) and IBS-QOL questionnaire. Pain perception during CTC was quantified using the visual analog scale (VAS) at six time points during the CTC as follows: (1) before CTC, (2) immediately after carbon dioxide gas injection, (3) until the injection pressure reached a plateau (18 mmHg), (4) in the prone position after carbon dioxide gas injection, (5) in the supine position after carbon dioxide gas injection, and (6) after CTC. We also evaluated the association between the VAS and IBS-SS scores.

Results

One hundred twenty-three subjects who underwent CTC were enrolled in this study. Thirteen subjects were excluded because of incomplete questionnaires (n = 10) or a diagnosis of colorectal cancer with CTC (n = 3). Fifteen patients were diagnosed as having IBS on the basis of the Rome IV criteria for IBS. Patients with IBS were classified into the following groups: IBS with diarrhea (IBS-D, n = 1), IBS with constipation (IBS-C, n = 3), mixed IBS (IBS-M, n = 3), and unspecified IBS (IBS-U, n = 8). No significant differences in background characteristics, including age, sex, alcohol consumption, and smoking habit, were found between the IBS and control groups. The volume of carbon dioxide gas injected during CTC did not show a significant difference between the two groups. The total colon length was not significantly different between the two groups. The VAS score of the IBS groups was significantly higher than that of the control group at two time points, (2) immediately after carbon dioxide gas injection (p < 0.01) and (3) until the injection pressure reached a plateau (18 mmHg; p < 0.01). The maximum VAS score during CTC was also significantly higher in the IBS groups than in the control group (p < 0.05). Although the IBS-SS score was significantly higher in the IBS groups than in the control group, we found no significant correlation between the VAS and IBS-SS scores in the IBS groups. The IBS-QOL score also did not show any significant correlation with the VAS score.

Conclusion

Our study indicates that pain perception evaluated using the VAS during CTC might be a potential diagnostic method for IBS. Further study is necessary to clarify the association between pain perception induced by CTC and IBS severity.