Introduction

The low incidence of APC gene mutations (less than 30%) in small bowel adenocarcinoma (SBA) suggests that the adenoma-carcinoma-sequence is not the main carcinogenic mechanism. However, the presence or absence of activation of the Wnt/β-catenin signaling pathway, which is important in the adenoma-carcinoma-sequence, has not been sufficiently investigated in SBA. Therefore, we examined gene mutations involved in the Wnt/β-catenin pathway and their downstream target gene products in SBA.

Aims & Methods

We examined 30 surgical resections from patients with primary SBA. SBA genomic alterations were analyzed by targeted next-generation sequencing (NGS). DNA mismatch repair (MMR) status was determined by immunostaining for all MMR proteins; MLH1, MSH2, MLH6, and PMS2. In addition, immunostaining for cyclin D1, c-myc, and β-catenin was performed to compare the results of NGS. Nuclear/cytoplasmic or loss of membranous β-catenin staining in cancer cells was defined as aberrant β-catenin immunostaining.

Results

The main genomic alterations found in SBA tumors were TP53 (56.7%), followed by KRAS (33.3%), APC (16.7%), PIK3CA (16.7%), CTNNB1 (10%), BRAF (6.7%), and CDKN2A (6.7%). Deficient MMR tumors were observed in 20% of patients. APC mutations were significantly higher in deficient MMR tumors than in proficient MMR tumors (P=0.041). On the other hands, CTNNB1 mutations were not found in deficient MMR tumors. No cases exhibited both the APC and the CTNNB1 mutations. Aberrant β-catenin immunostaining in cancer cells was observed in 12 out of 30 cases (40%). All three CTNNB1 mutation cases were associated with aberrant β-catenin staining, whereas only 1 of 5 APC mutation cases had aberrant β-catenin staining. The remaining 8 cases with aberrant β-catenin staining had neither APC nor CTNNB1 mutations. Cyclin D1, a representative target protein of the Wnt/β-catenin pathway, was positive in cancer cells in 18 (60%) of the cases. C-myc was positive in cancer cells in 6 (20%) cases. Of the 5 cases with APC mutations, cyclin D1 was positive in two cases and c-myc was positive in one case. Three cases were negative for both cyclinD1 and c-myc, but were associated with MMR deficiency and TP53 mutations. Of the three cases with CTNNB1 mutations, cylclin D1 was positive in two cases and c-myc was positive in one case. All three cases had proficient MMR. Two of the three cases did not have TP53 nor KRAS mutations.

Conclusion

The Wnt pathway-associated gene mutations in SBA were APC and CTNNB1, with one or the other found in 26.7% of cases examined. This frequency is much lower than in colorectal cancer, consistent with previous reports. In addition, 3 out of 5 cases with APC mutations showed normal membranous staining for β-catenin, cyclin D1-negative, and c-myc-negative, suggesting that the Wnt pathway is less activated in these three cases. In addition, these three cases had TP53 mutations and were MMR deficient. This suggests the possibility that APC mutations do not necessarily contribute directly to the carcinogenesis of SBA. On the other hand, the staining abnormality of β-catenin, a key component of the Wnt/β-catenin signaling pathway, suggests that this pathway is activated in half of SBA cases. These results indicate that the Wnt/β-catenin pathway may be activated or deregulated by mechanisms other than APC and CTNNB1 mutations in SBA.

Introduction

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease with unknown causes. Patients experience periods with active disease and symptoms such as diarrhoea, pain and weight loss. Little is known about environmental factors that trigger flare-ups, including the effects of commonly used medications. Recent studies suggest a link between microbial factors and IBD, making it important to investigate the impact of antibiotics on flare-ups.

Aims & Methods

We aimed to investigate whether certain antibiotics increase the risk of flares in patients with IBD. We utilized a previously described¹ cohort of all patients with IBD in Denmark between 1974 and 2018. The cohort is based on the Danish Nationwide Patient Registry, which registers all healthcare related visits, treatments and procedure on an individual level. We utilized data between 1994 and 2018 and two distinct cohorts was created for the purpose of identifying flares. The first cohort was characterized by having an IBD-related hospital stay. The second cohort was characterized by experiencing a flare of IBD in need of systemic steroids. Patient were matched 1:5 using K-nearest neighbour. Antibiotics were grouped into the 3rd level of the Anatomical Therapeutic Chemical (ATC) classification system, with anthelmintics grouped into the 2nd level due to low numbers and all given within 60 days before the outcome. Logistic regression analysis was used to calculate odds ratios (ORs) with a 95% confidence interval (95% CI), with adjusting variables including year of remission/flare, sex, age at diagnosis, year of diagnosis, type of IBD, socioeconomic status², use of 5-ASA, use of budesonide, use of immunosuppressants, and use of subtypes of biologics.

Results

There were in total 69,908 IBD patients in the original cohort. After applying the abovementioned algorithm, a total of 15,636 and 5,178 patients were included in the cohort for hospitalisation and steroid use, respectively.
Using a multivariate logistic regression model, both cohorts observed a significant increase in odds ratios for certain antibiotics in relation to hospitalization and steroid course. Specifically, for the need of a course of steroids, quinolones (OR 3.83 (95% CI: 2.73-5.35)), antimycotics (OR 2.30 (95% CI: 1.53-3.40)), agents against amoebiasis and protozoal (OR 2.06 (95% CI: 1.39-3.01)), betalactam antibiotics (OR 1.35 (95% CI: 1.10-1.66)), and intestinal anti-infectives (OR 2.12 (95% CI: 1.08-3.98)) were associated with an increased risk for a flare requiring steroids.
Regarding the need for an IBD-related hospitalization, agents against amoebiasis and protozoal (OR 3.48 (95% CI: 2.72-4.44)), quinolones (OR 3.10 (95% CI: 2.48-3.86)), intestinal anti-infectives (OR 2.42 (95% CI: 1.54-3.76)) and antimycotics (OR 1.58 (95% CI: 1.17-2.12)) were all found to be significantly associated.

Conclusion

This study provides evidence that certain types of antibiotics increase the risk of flare-ups in patients with IBD. Quinolones, antimycotics, agents against amoebiasis and protozoal, betalactam, and intestinal anti-infectives were all associated with increased odds ratios for hospitalization and a need for a course of steroids. These findings highlight the importance of carefully considering the use of antibiotics in IBD patients and the need for further research on the effects of different antibiotics on disease progression.

References

¹ Lo B, Zhao M, Burisch J. Identifying patients with inflammatory bowel disease in the Danish National Patient Register. Dan Med J. 2023 Mar 27;70(4):A07220458. PMID: 36999818.
² https://www.dst.dk/en/Statistik/dokumentation/nomenklaturer/socio

Disclosure

An unrestricted grant was received from the Aage og Johanne Louis-Hansens Fond to support this study.

Introduction

Recently, artificial intelligence-based computer-aided detection (CADe) for colonoscopy is garnering significant attention due to its effectiveness in increasing adenoma detection rate (ADR). However, theoretically, CADe system cannot decrease exposure error which polyps obscured by an object. In this regard, computer-aided quality improvement (CAQ) which expects to induce the meticulous mucosal inspection and leading to a reduction of blind spot area. In this study, we developed and evaluated CAQ for colonoscopy.

Aims & Methods

This was a single center, retrospective study from period April 1, 2022 to February 25, 2023. We randomly extracted colonoscopy videos and created 18,922 training images. Quadrant images were made from one image and three endoscopists annotated the following scores; i) appropriateness for mucosal inspection, ii) appropriate distance, and iii) presence of blind area in the field of view (e.g., fold or flexure). We conducted supervised machine learning using annotated images. The CAQ deployed multi-head deep convolutional neural network model which can output multiclass prediction from one image. Consequently, the CAQ system outputs aforementioned score from whole colonoscopy video. To validate its performance, we retrospectively analyzed colonoscopy procedures performed by seven endoscopists using the CAQ. We compared calculated CAQ model scores and expertise of endoscopists.

Results

29 videos were included as validation samples (8 videos were performed by non-expert endoscopists) As a result, there was a significant difference in the proportion of appropriate images during the examination between experts and non-experts (median 56% vs. 49%, p=0.005, Mann–Whitney U test) and there was also a significant difference in the evaluation score of the distance between the colon mucosa and the endoscope (median 4.2 vs. 3.2, p=0.0004, Mann–Whitney U test). In addition, there was a significant difference in the scores evaluating the presence of blind areas in the field of view (median 1.6 vs. 1.2, p=0.0007, Mann-Whitney U test).

Conclusion

In this study, developed CAQ system could quantify the skill of the endoscopists. Such CAQ would be expected to standardize the observation technique of colonoscopy.

Introduction

To prevent stent migration during EUS-HGS, intra-scope channel release technique is important, but are unfamiliar to non-expert hands. The self-expandable metal stent (SEMS) is an additional factor to prevent stent migration. However, no comparative studies of laser-cut and braided types during EUS-HGS have been reported.

Aims & Methods

The aim of this study was to compare the distance between the intrahepatic bile duct and stomach wall after EUS-HGS among laser-cut- and braided-type SEMS. To evaluate stent anchoring function, we measured the distance between the hepatic parenchyma and stomach wall before EUS-HGS, one day after EUS-HGS, and 7 days after EUS-HGS.　Also, propensity score matching was performed to create a propensity score for using Laser cut type group and Braided group with a logistic regression model.

Results

A total 144 patients were enrolled in this study. Among them, 24 patients underwent EUS-HGS using a laser-cut-type SEMS, and 118 patients underwent EUS-HGS using a braided-type SEMS. EUS-HGS using the laser-cut-type SEMS was mainly performed by non-expert endoscopists (n=21). However, EUS-HGS using braided-type SEMS was mainly performed by expert endoscopists (n=98), showing a significant difference. The distance after 1 day was significantly shorter with the laser-cut-type group (2.91 ± 1.88 mm) compared with the braided-type group (8.19 ± 6.07 mm). In addition, this distance remained significantly shorter in the laser-cut type group compared with the braided-type group after 7 days.　Although these results were similar after propensity score matching analysis, the distance between hepatic parenchyma and stomach after 7 days was increased 4mm compared with the distance after 1 day in Braided group. On the other hand, in Laser cut type group, the distance after 1 day and 7 days was almost same.

Conclusion

In conclusion, EUS-HGS using a laser-cut-type SEMS may be safe to prevent stent migration, even in non-expert hands, compared with a braided-type SEMS, although a randomized trial is warranted.

Disclosure

None

Introduction

Balloon dilation and plastic stent deployment have been performed as hepaticojejunostomy stricture (HJS) treatment techniques by PTBD or under DB-ERCP guidance. Although these techniques have shown favorable clinical results, the treatment period can be long because stent deployment is required. In addition, HJS may recur even after treatment because the scar tissue itself remains. To overcome these challenges, we developed an transluminal antegrade piecemeal dilation technique (TAPD) for treating HJS. The aim of this study was to evaluate the technical feasibility and safety of this technique in terms of the pre- and post-cholangioscopic findings.

Aims & Methods

This retrospective study included consecutive patients who were complicated with symptomatic HJS between November and February 2022. The primary outcome of this study was the technical success rate of TAPD using a drill dilator. Technical success was defined as resolution of the HJS, based on the cholangioscopic findings. The secondary outcome was adverse events associated with TAPD such as bleeding or perforation.

Results

TAPD was attempted at around 11 days after EUS-HGS in 19 patients. Among the 19 patients, passage of the guidewire across the HJS into the intestine was unsuccessful in 4 patients, and the technical success rate of this procedure was 78.9%. TAPD was successful in all 15 patients in whom passage of the guidewire was achieved. After TAPD, cholangioscopy identified no bleeding or perforation in any patient. During the follow-up period, no recurrence of HJS was observed in any patient who underwent TAPD.

Conclusion

In conclusion, TAPD appears to be technically feasible and safe. Although it is necessary to conduct a randomized trial in comparison with other methods, with long-term follow up, TAPD may be a useful option for the treatment of HJS.