Introduction

Alterations in body composition and metabolic factors may serve as a potential biomarker for early-detection of pancreatic ductal adenocarcinoma (PDAC).

Aims & Methods

This study aimed to capture the longitudinal changes occurring in body composition and metabolic factors preceding a diagnosis of PDAC. All patients (≥18 years) diagnosed with PDAC between 2000 and 2021 were identified. We collected data on demographics, comorbidities, PDAC characteristics, all abdominal CT scans and blood-based markers up to 3 years prior to date of diagnosis (index date). We applied a fully-automated abdominal segmentation algorithm previously developed by our group (Weston et al. Radiology 2019 [1]) for three-dimensional quantification of body composition on CT scans. Longitudinal trends of body composition and laboratory markers prior to a diagnosis of PDAC were estimated by linear mixed models and visualized using spline regression.

Results

We included 1,825 PDAC patients in body composition analysis, of which 581 (31.8%) had ≥2 pre-diagnostic CT exams. For analysis of longitudinal trends of blood-based markers, 4,846 patients were included. Mean age at diagnosis was 68.4 (SD 11.3) years, 43.6% were female and the mean BMI was 27.0 (SD 5.5). The distribution of PDAC stage was as follows: 12.5% stage I, 32.6% stage II, 19.7% stage III, and 35.2% stage IV. Prior to a PDAC diagnosis, we observed significant decreases in visceral fat volume, subcutaneous fat volume, bone volume, and a variety of blood markers including low-density lipoprotein and hemoglobin (Table 1). Concurrently, patients developed significant increases in HbA1c, fasting blood glucose, high-density lipoprotein and white blood cells prior to a clinical PDAC diagnosis. Most body composition and metabolic markers showed a linear decreasing or increasing trend over time to diagnosis of PDAC.

Table 1. Trends of body composition and laboratory markers over time prior to a diagnosis of PDAC estimated by linear mixed models.

Conclusion

This study identified significant alterations in a variety of soft tissue and metabolic markers that occur in the development of PDAC. These metabolic changes may become apparent several years before diagnosis, which may serve as a significant window of opportunity for early detection.

References

1. Weston AD, Korfiatis P, Kline TL, Philbrick KA, Kostandy P, Sakinis T, Sugimoto M, Takahashi N, Erickson BJ. Automated Abdominal Segmentation of CT Scans for Body Composition Analysis Using Deep Learning. Radiology. 2019 Mar;290(3):669-679. doi: 10.1148/radiol.2018181432. Epub 2018 Dec 11. PMID: 30526356.

Disclosure

On behalf of all authors, I declare no conflicts of interest.

Introduction

Colorectal neuroendocrine tumors (NETs) and polyps have similar endoscopic manifestations and are easily misidentified. Due to the low incidence of NETs, it is difficult to obtain adequate images to fit deep-learning models. This study introduced a few-shot learning (FSL) model for the ternary classification of NETs and polyps on endoscopic images.

Aims & Methods

Three classes of endoscopic images (56 serrated lesions and polyps [SLPs], 86 traditional adenomas and 53 NETs) were collected from three datasets. First, three images from each class were randomly selected for Support Set (SS), while others for Query Set (QS). Second, ResNet50 V2 was pretrained based on ImageNet and then on esophageal endoscopic images Third, imaging eigenvectors were extracted based on a dual-pretrained model. Fourth, the Euclidean distances to the nine SS images were calculated for each QS image. Finally, a k-nearest neighbor classifier was used for classification based on Euclidean distances. The proposed FSL model was tested in three rounds.

Results

The performance of the FSL model (macro-area under the curve [AUC], 0.731; macro F1-score, 0.674; Matthews Correlation Coefficient [MCC], 0.526; Kappa, 0.523) was better than that of the traditional ResNet50 V2, junior endoscopist, and senior endoscopist. When identifying NETs, the proposed FSL model achieved the highest accuracy 0.823, sensitivity 0.653, precision 0.673 and F1-score 0.659, whereas the senior endoscopist achieved the highest specificity 0.904.

Conclusion

This study presented a FSL method based on transfer learning and metric learning to distinguish between SLPs, adenoma, and NETs on endoscopic images. This suggests that FSL might be an effective method for computer-aided diagnosis of rare diseases.

Introduction

Small bowel adenocarcinoma (SBA) are rare, but their incidence is increasing. Early diagnosis of SBA remains elusive, so that about one-third of patients are initially diagnosed with distant metastases. In clinical practice, regimens used for SBA parallel those commonly administered in the adjuvant setting for colorectal cancer, owing to its anatomic proximity. However, genomic profiling of SBA has been shown to be distinct from colorectal cancer through comprehensive analysis of genomic alterations. Therefore, it is vital to establish a distinct chemotherapy regimen for SBA based on its molecular pathological characteristics. Claudin-18 plays a key role in constructing tight junctions and altered claudin-18 expression has been documented in various human malignancies. On the basis of this, both monoclonal antibodies and claudin-18.2-specific chimeric antigen receptor engineered T-cells have been recently developed and employed in several clinical trials, showing promising results in the treatment of advanced gastroesophageal and pancreatobiliary tract cancers. However, little is known about the clinicopathological significance of claudin-18 expression in SBA.

Aims & Methods

To explore the localization of claudin-18 in human SBA tissue and draw comparisons and determine the relationship between their expression and clinicopathological factors, and genomic alterations.
We examined 50 surgical resections from patients with primary SBA for immunohistochemical analyses of claudin-18, CK7, CK20, CD10, CDX2, MUC2, MUC5AC, and MUC6 expression. DNA mismatch repair (MMR) status was defined by immunostaining for all MMR proteins; MLH1, MSH2, MLH6, and PMS2. Both MUC 2 and CD10 are markers of intestinal type tumors, whereas MUC5AC and MUC6 are markers of gastric type tumors. Tissue samples showing both gastric and intestinal phenotypes were classified as gastrointestinal type tumors, whereas those showing neither gastric nor intestinal phenotype expression were classified as null type tumors. In addition, genomic profiling was performed on 31 patients using targeted next-generation sequencing.

Results

Claudin-18 expression was observed in 46% of SBA patients. Claudin-18 expression was positively associated with cytokeratin 7 (P=0.003) and MUC5AC (P=0.020) expression, whereas it was negatively associated with MUC2 (P=0.010), CD10 (P=0.014), and CDX2 (P=0.003) expression. Tumor mucin phenotypes included gastric type (n=9), intestinal type (n=20), gastrointestinal type (n=17) and null type (n=4). Claudin-18 was more frequently expressed in gastric type (100%) than in intestinal type (30%) phenotypes (P=0.001). GNAS mutations (N=4) were found in only claudin-18 positive SBA patients, although the difference was not significant. Claudin-18 expression did not correlate with patient age at diagnosis, patient gender, site, histological type, depth of invasion, lymph node metastasis, distal metastasis, TNM stage, and MMR status. However, claudin-18 expression correlated with worse progression free survival.

Conclusion

Claudin-18 expression is associated with gastric immunophenotype and with worse progression free survival. These findings suggest that claudin-18 may be a potential therapeutic target in certain SBA cases.

Introduction

Gastric adenoma is recognized as a premalignant lesion.¹Much of the literature lumps all adenomas together with different classifications. These are few western reports regarding the prevalence, associated risk factors and outcomes of endoscopic management of different subtypes of gastric adenoma.

Aims & Methods

Aims: The aim of this study is to determine the prevalence, potential predictors, and outcomes of endoscopic management of the different subtypes of gastric adenoma.
Methods: Of 162 consecutive patients who underwent endoscopic resection for gastric lesions between 2017 and 2022 at our center, 79 patients were enrolled. All the hyperplastic polyps (n=37) and subepithelial lesions (n=46) were excluded. The patient clinical characteristics, endoscopic and histopathological features of gastric lesions were retrospectively collected. Patients were divided according to the histological types of gastric adenoma into 4 groups: intestinal group (n= 49), foveolar group (n= 23),pyloric group (n= 6) and oxyntic group (n=1). We statistically compared the clinical and endoscopic features of the three groups. In addition to the analysis of the outcomes of endoscopic resection of gastric adenomas.

Results

Of the 79 patients with a mean follow-up of 2622 months, 51 patients were males (65 %) and 28 patients were females (35%). Forty-nine patients (49/79,62%) had intestinal adenoma, 23 patients (29%) showed foveolar adenoma, 6 patients (8%) developed pyloric adenoma and only 1 patient (1%) had oxyntic adenoma. The mean age was significantly older in the intestinal group (71 ± 13 years vs. 64 ± 16 years vs. 58 ± 18 years, p = 0.03). Intestinal adenomas were significantly associated with family history of gastric adenocarcinoma (14% vs. 4% vs. 0%, p = 0.01) and history of statin intake (39% vs. 26% vs. 0%, p = 0.04).Foveolar adenomas were significantly associated with multiple lesions (≥3 lesions) (p < 0.001) and 0-IIa+IIc Paris classification (6/23, 26%). the size of largest polyp was significantly higher among pyloric group (28 ±15, p= 0.00). Among intestinal group, 33/49 patients (67%) had atrophic gastritis. 82% of the adenomas were resected by ESD with histologically complete resection (R0) in 72/79 patients (91%). Although the difference was not statistically significant (p = 0.4), adenocarcinoma was most frequently encountered among the intestinal adenoma group (17/49, 35%). The post endoscopic resection outcome was comparable among 3 groups with overall recurrence rate (group1:8% vs. group 2:17% vs group 3:17%, P = 0.07) with a comparable mean time to recurrence among three groups (21 ± 17 months vs. 20±17months vs. 14 months, p=0.8). Family history of gastric adenocarcinoma (HR=1.33, p< 0.001) and active helicobacter pylori infection (HR=1.14, p < 0.001) were identified as independent predictors of recurrence after endoscopic resection of different gastric adenoma. Among baseline endoscopic characteristics, polyp size ³ 30mm(HR= 2.04, p< 0.001), more than 3 polyps (HR=1.51, p<0.001), lesser curvature as lesion location (HR=1.72, p< 0.001) and morphology as Paris classification IIc are potential predictors of post resection recurrence. In addition to specimen size ³ 15mm (HR=2.19, p< 0.001) and T1b as lesion histology (HR=2.07, p< 0.001), in the histopathological examination.

Conclusion

The present study clarifies the endoscopic and histopathological characteristics of different gastric adenomas, in addition to the potential predictive factors for each subtype. Potential predictors of recurrence after endoscopic resection emphazie the importance of endoscopic follow up.

References

1. Fujiwara, Y. et al. Diagnosis of borderline adenomas of the stomach by endoscopic mucosal resection. Endoscopy 28, 425–430 (1996).

Introduction

A low incidence of eosinophilic esophagitis (EoE) in children in the North Denmark Region (NDR) were measured in 2007-2017. Few of the children diagnosed before 2017 were treated to remission suggesting a lack of awareness. While there currently are no guidelines for treating EoE in Denmark, a new English guideline was published in 2022 renewing focus on the disease.

Aims & Methods

The aim of this study was to measure the difference of current Danish clinical practice for treatment and follow-up of EoE children in the NDR with the new English guideline from the British Society of Gastroenterology (BSG) and the British Society of Pediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN). This retrospective, register-based DanEoE cohort study included 31 children diagnosed with EoE between 2007–2021 in NDR. Medical records were reviewed and information about treatment and follow-up were collected.

Results

In 32% of the children with EoE in the NDR, first-line treatment initiated corresponded with the recommendations in the new English guideline. One in 6 children were never started on any treatment even though treatment always is recommended. Symptomatic follow-up was completed in 77% (24/31) of children and 85% (11/13) of the children after 2017. Histologic follow-up within 12 weeks was completed in 13% (4/31) of the children and 15% (2/13) of the children after 2017. Combined symptomatic and histologic remission after first-line treatment was achieved in 6% (2/31).

Conclusion

In Denmark focus on improving EoE treatment and follow-up for children is needed, as there is a significant difference between current clinical practice and the recommendations in the new English guideline.

References

Hollænder M, Terkelsen JH, Kramme F, Bredal K, Kragholm K, Dalby K, et al. The incidence of eosinophilic oesophagitis in 2007-2017 among children in North Denmark Region is lower than expected. BMC Pediatr. 2022 Apr;22(1):183.
Dhar A, Haboubi HN, Attwood SE, Auth MKH, Dunn JM, Sweis R, et al. British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults. Gut. 2022 Aug;71(8):1459–87.