Introduction

Recent evidence suggests that Computer-Aided Detection (CADe) systems, when used alongside mucosal-exposure devices, may enhance adenoma detection during colonoscopy. This study evaluates whether the integration of CADe with the GEYE balloon, an endoscope with a reusable on-demand inflatable balloon at the tip, enhances adenoma detection in a fecal immunochemical test (FIT)-based colorectal cancer screening program.

Aims & Methods

Subjects aged 50-74 who tested FIT-positive as part of a national colorectal cancer (CRC) screening program, were randomized to undergo colonoscopy with either CADe alone (CADEYE, Fujifilm Co., Tokyo, Japan) or CADe combined with the GEYE balloon (G-EYE 760R, Fujifilm Co., Tokyo, Japan), performed by accredited endoscopists. The primary outcome measures included the rate of "high-risk" individuals, who need intensive surveillance, as defined by the ESGE criteria (> 5 low risk adenoma, at least one adenoma with high-risk features, any serrated polyp ≥ 10 mm or with dysplasia) and the adenoma detection rate (ADR). Based on prior research, the study was intended to include 600 subjects.

Results

From May 2023 to April 2024 (ongoing), 479 subjects were randomized; 34 were subsequently excluded due to incomplete examination (4), inadequate preparation (12), or malfunctioning of the G-EYE balloon or CADe (18). The remaining 445 subjects were enrolled in the study (median (IQR) age 61 y/o (58-66); 216 men). Of them 229 and 216 underwent CADe colonoscopy and CADe+GEYE colonoscopy, respectively. No significant differences were observed between the two groups in terms of patient characteristics, cleansing levels, insertion times, overall withdrawal times, or inspection durations. At interim analysis, the rate of "high-risk" individuals post-colonoscopy was 26.3% (95% CI: 20.9-32.4%) with CADe and 20.8% (95% CI: 15.4-26.3%) with CADe+GEYE. The ADR was 60.7% (95% CI: 54.4-67%) for CADe and 54.2% (95% CI: 47.5-60.8%) for CADe+GEYE, respectively. Secondary outcomes, including Polyp Detection Rate (PDR), Sessile Serrated Lesion Detection Rate (SSLDR), and Adenoma Per Colonoscopy (APC), showed no significant differences.

Conclusion

Data suggest that adding GEYE to CADe does not significantly increase the adenoma detection. Although the data are still not definitive, we can hypothesize that a “ceiling effect” due to the high detection rate of lesions with CADe have marginalized the impact of mucosal-exposure device.

Introduction

The therapeutic armamentarium for inflammatory bowel disease (IBD) is rapidly increasing recent years with newer therapies such as vedolizumab (VDZ). Their effectiveness has already been demonstrated against placebo, but head-to-head trials compared to tumour necrosis factor alpha inhibitors (anti-TNF) are scarce.

Aims & Methods

Aim: To compare the effectiveness of VDZ versus anti-TNF in bio-naïve IBD patients in a real world setting.
Methods: A retrospective monocentric study was performed in IBD patients treated with VDZ and anti-TNF at a Belgian University Hospital, from January 2018 to June 2021 with follow-up until December 2021. Primary endpoints considering efficacy after induction and after 1 year of therapy were: clinical response (CRp) and remission (CRm), biochemical response (BRp) and remission (BRm) and endoscopic response (ERp) and remission (ERm). Secondary endpoint was treatment survival during follow-up. For assessment of risk factors influencing efficacy and treatment survival, a multivariate logistic regression and Cox regression model were applied. Propensity scores for VDZ vs. anti-TNF were weighted for age at start biological, IBD type, perianal disease activity, disease duration and previous IBD-related intestinal resection.

Results

In total, 42 patients received VDZ and 57 anti-TNF. At baseline, the VDZ group had an older median age (38 vs. 31 years, P=0.024), longer disease duration (P=0.017) and more moderate to severe comorbidities (21.4% (9/42) vs. 0% (0/57), P<0.001). In the anti-TNF group, percentage of CD patients was higher (77.2% (44/57) vs. 57.1% (24/42),P=0.034), patients had more upper GI, penetrating or stricturing disease (P=0.013 for location and P=0.004 for behavior), perianal disease (P=0.034) and used more immunomodulators (IMM) during treatment (52.6% (30/57) vs. 16.7% (7/42), P<0.001). After treatment induction, CRp (P=0.311) and CRm (P=0.216) rate was not significantly different. The anti-TNF group had a significantly higher BRp rate compared to the VDZ group (87.8% (43/49) vs. (23/34), P=0.026). After adjusting for propensity score, age, IBD type, systemic corticosteroid (CS) or IMM use, the higher rate of BRp remained (aOR 3.83 [1.01-14.60], P=0.049). Similar results were found for BRm (87.8% (43/49) vs. 67.6% (23/34), P=0.026). After adjustment for the same confounders, the higher rate of BRm in the anti-TNF group remained (aOR 3.83 [1.01-14.60], P=0.049). No significant difference was seen for ERp (P=1.000) and ERm (P=0.338). After 1 year, univariate analysis showed no significant difference for CRp (P=0.736) and CRm (P=0.404), nor for BRp (P=0.907) and BRm (0.890) or for ERp (P=0.163) and ERm (P=0.533). Treatment survival using Cox regression model with adjustment for propensity and IMM or CS use, showed no significant longer treatment duration for anti-TNF compared to VDZ (aHR 0.947 [0.36-2.49], P=0.913).

Conclusion

In this tertiary real-world cohort of bio-naïve patients with IBD, anti-TNF and VDZ showed a similar efficacy, with an advantage of anti-TNF regarding onset of action.

Introduction

New methods are urgently needed to detect pancreatic ductal adenocarcinoma (PDAC) at an earlier stage to improve outcomes.^{1, 2} We have previously reported six protein N-glycosylation traits (NGTs) and further grouped these into three biologically distinct ones to discriminate PDAC patients from healthy controls with an area under the curve (AUC) of 0.81-0.88.³ A subsequent longitudinal study revealed glycosylation differences up to 50 months prior to diagnosis, indicating potential for early detection.⁴ However, external validation is needed to determine accuracy of this biomarker panel. Moreover, it is unknown whether this panel can differentiate PDAC in a diverse group that resembles clinical practice better. Therefore, this study aims to validate the biomarker panel in a heterogeneous cohort.

Aims & Methods

Protein N-glycans in prospectively collected plasma samples from Mayo Clinic were analyzed by mass spectrometry at the Leiden University Medical Center using a semi-automated preparation protocol.⁵ Glycosylation profiles were determined and compared between PDAC cases and controls. The control group consisted of imaging-confirmed pancreatic disease-negative controls and individuals with benign pancreatic diseases, including (non)-mucinous cysts and pancreatitis. Logistic regression was performed to calculate odds ratios (ORs) for the six previously reported protein NGTs. Additionally, AUC, sensitivity and specificity were calculated to determine the accuracy of the three biologically distinct NGTs (antennarity (CA4), sialylation (A3F0L), and fucosylation (CFa)) in discriminating PDAC cases from controls.

Results

We included 232 individuals, of whom 42 (18.1%) were diagnosed with PDAC, and 190 (81.9%) served as controls. Among controls, 59 (31.1%) were pancreatic disease-negative and 131 (68.9%) had benign pancreatic diseases. Median age of PDAC cases and controls was 71.7 (IQR=14.5) and 65.5 years (IQR=17.6), respectively. Among PDAC cases, 19 (45.2%) were female, and 106 (52.2%) among controls. The BMI in PDAC cases and controls was equal (26.8 (IQR=7.0) and 26.6 (IQR=7.6), respectively). Table 1 shows ORs for the six NGTs and PDAC. The AUC for the three biologically distinct traits was 0.77 (95% CI: 0.69-0.86), with a sensitivity of 0.81 (95% CI: 0.69-0.93) and specificity of 0.70 (95% CI: 0.64-0.76). When comparing PDAC cases to pancreatic disease-negative controls, the AUC was 0.83 (95% CI: 0.74-0.92), with a sensitivity of 0.79 (95% CI: 0.64-0.90) and specificity of 0.80 (95% CI: 0.69-0.90).

Conclusion

Distinctive NGTs from plasma protein differentiate PDAC from non-PDAC in a diverse group, consisting of cystic pancreatic diseases and pancreatitis. This panel holds potential for future early detection methods.

References

1. Klatte DCF, Wallace MB, Löhr M, Bruno MJ, van Leerdam ME. Hereditary pancreatic cancer. Best Pract Res Clin Gastroenterol. 2022;58-59:101783.
2. Goggins M, Overbeek KA, Brand R, Syngal S, Del Chiaro M, Bartsch DK, et al. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut. 2020;69(1):7-17.
3. Vreeker GCM, Hanna-Sawires RG, Mohammed Y, Bladergroen MR, Nicolardi S, Dotz V, et al. Serum N-Glycome analysis reveals pancreatic cancer disease signatures. Cancer Med. 2020;9(22):8519-29.
4. Levink IJM, Klatte DCF, Hanna-Sawires RG, Vreeker GCM, Ibrahim IS, van der Burgt YEM, et al. Longitudinal changes of serum protein N-Glycan levels for earlier detection of pancreatic cancer in high-risk individuals. Pancreatology. 2022;22(4):497-506.
5. Vreeker GCM, Nicolardi S, Bladergroen MR, van der Plas CJ, Mesker WE, Tollenaar R, et al. Automated Plasma Glycomics with Linkage-Specific Sialic Acid Esterification and Ultrahigh Resolution MS. Anal Chem. 2018;90(20):11955-61.

Introduction

Anti-tumour necrosis factor-alpha (anti-TNF-alpha) therapy is an effective treatment for the management of Crohn’s disease (CD). However, treatment failure is common.

Aims & Methods

The aim of this study was to identify predictors of anti-TNF-alpha therapy failure.
Retrospective single-center study including anti-TNF-alpha naïve patients with CD, who started on intravenous infliximab, between January 2019 and December 2021. Biochemical parameters included erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), faecal calprotectin, infliximab serum concentrations and the presence of antibodies to infliximab (ATI). Anti-TNF-alpha therapy failure was defined as the development of ATI at 6 and 12 months, absence of clinical response at 6 months, absence of clinical remission or of objective response at 12 months. Clinical response was defined as a reduction in Harvey-Bradshaw index (HBI) of ≥ 3 points comparing with initial value or HBI < 5 points if initial HBI ≥ 7 points and clinical remission as HBI ≤ 4 points. Objective response was assessed by endoscopic studies, defined by improvement of mucosal inflammation and absence of deep ulcerations, or imaging, defined as improvement in bowel wall thickness, inflammatory fat, mural blood flow and hyper-enhancement.

Results

A total of 53 CD patients were included, 30 were female (56.6%), with a mean age at the beginning of treatment of 39 ± 2 years. Considering the Montreal classification, 31 patients had ileal disease (58.5%), 7 colonic (13.2%) and 15 ileocolonic disease (28.3%); 22 patients had nonstricturing, nonpenetrating disease (41.5%), 22 stricturing (41.5%) and 9 penetrating disease (17.0%). Eleven patients had perianal disease (20.8%). A total of 26 patients (49.1%) were treated with combination of anti-TNF-alpha and immunomodulatory therapy (thiopurine or methotrexate). Anti-TNF-alpha therapy failure occurred in 21 patients (39.6%). At 6 months, the development of ATI occurred in 6 patients (11.3%) and absence of clinical response in 9 patients (17.0%). At 12 months, absence of clinical remission was seen in 13.6% of patients and absence of objective response in 27.0% of patients.
At 6 months, the development of ATI was significantly higher in patients with lower infliximab serum concentrations at week 14 (with antibodies 5.9±3.2 µg/mL vs without 14.3±7.7 µg/mL, p<0.001). Additionally, the development of ATI was significantly higher in patients with a higher initial value of ESR (with antibodies median 35 vs without median 13, p=0.045). The infliximab serum concentrations at week 14 (AUC 0.828; p=0.009; sensitivity 0.833 and specificity 0.404 for values ≤11.6) and the initial value of ESR (AUC 0.754; p=0.045; sensitivity 0.833 and specificity 0.468 for values ≥15) had very good and good discriminative capacity, respectively, in predicting the development of ATI. No statistically significant differences were found in initial values of CRP and faecal calprotectin, between both groups. Moreover, the other definers of anti-TNF-alpha therapy failure were not associated with the combination with immunomodulatory therapy, infliximab serum concentrations at week 14 or initial values of ESR, CRP and faecal calprotectin.

Conclusion

Infliximab serum concentration after induction therapy is the most important factor in the development of ATI, influencing treatment response, regardless of the combination of anti-TNF-alpha therapy with immunomodulatory therapy. A higher initial value of ESR can also predict the development of ATI.