Introduction

Local endoscopic resection for early rectal cancer is increasingly used. For tumors extending into the muscularis propria (T2 carcinoma) a local resection is a suboptimal oncological treatment. Discrimination between T1 and T2+ rectal cancer is therefore important. Optical diagnosis lacks specificity, MRI. EUS has sufficient resolution to visualize bowel wall layers, but interpretation is difficult and subjective. In this pilot study we investigated whether automated imaging analysis (AI), which segemtates the bowel wall layers and the tumor, could be an aid to the performance of EUS in staging early rectal cancer.

Aims & Methods

In this single-center study, L-EUS media, optical and pathological data were prospectively collected from patients referred for local resection. EUS images were manually segmented by FtB. This dataset was used to train a Convoluted Neural Network (CNN) to assign a label (background, lesion / mucosa, submucosa, and muscularis propria) to every pixel. We used an U-Net architecture. CNN performance was increased by data augmentation using affine random transformations.
For the training of our CNN we used cross validation to divide the data set in a training, testing and validation set. We trained our CNN 16 times with every time a different testing set of 5 patients (and a different training and validation set of resp. 70 and 5 patients), this way we could use the entire data set to investigate the CNN performance.
Segmentation success of the trained CNNs was validated by calculating the Dice similarity index (DSI), the mean surface distance (MSD) and Hausdorff distance (HDD) between the automatic and manual segmentation.
In addition, the results of AI analyses were assessed from a clinical point of view, considering it as an aid for EUS interpretation. Overtly misinterpretated images were considered useles and were excluded in the clinical evaluation. Finally, the results were tested against pathology.

Results

We included 80 cases in whom 373 EUS images were manually segmented. The median MSD and HDD were resp. 3.2 and 17.7 pixel for the tumor, 3.4 and 24.7 pixel for the (sub)mucosa and 2.6 and 20.0 for the muscularis propria. The median DSI values for the tumor, (sub)mucosa, and muscularis propria were 0.82, 0.57 and 0.59 respectively. These values reflect good agreement between manual and automatic segmentation.
Clinical evaluated of AI images revealed usefull segmentations in 81% of cases. The sensitivity of automated segmentations for infiltration in the muscular wall was 83.0%; the specificity was 65%, and the accuracy 73%. These were static images only.

Conclusion

We found encouraging results with automatic segmentation based on relatively few static EUS images for the staging of early rectal cancer. Our results support exploration of automatic EUS segmentation to stage early rectal cancer, and improvement is expected when this tool is applied real-time on dynamic EUS imaging.

References

Kuwahara T, Hara K, Mizuno N, Haba S, Okuno N, Koda H, et al. Current status of artificial intelligence analysis for endoscopic ultrasonography. Dig Endosc. 2021;33:298–305.
Ronneberger O, Fischer P, Brox T. U-Net: Convolutional Networks for Biomedical Image Segmentation. Int Conf Med image Comput Comput Interv. 2015;234–41

Introduction

The estimated global prevalence of biopsy-confirmed celiac disease (CeD) is 0.7% and sero-positive prevalence is 1.4%. Differences in definitions of CeD cases and at-risk populations, as well as underdiagnosis, may affect accurate estimation of the size of the diagnosed CeD population. In this study, we calculated the 10-year prevalence of diagnosed CeD in the USA using different CeD case definitions and at-risk populations.

Aims & Methods

A prevalence analysis of CeD cases was conducted using data collected from the Optum Clinformatics^® Data Mart, a US claims database. Prevalence calculations were based on two different definitions of CeD cases. Case definition 1 included any of the following: 1) International Classification of Diseases (ICD)-9/-10 diagnostic codes for CeD (≥ 1 inpatient or ≥ 2 outpatient codes), 2) tissue transglutaminase immunoglobulin A (tTG-IgA) positive serology or 3) biopsy-confirmed CeD (defined as esophagogastroduodenoscopy [EGD] followed by an ICD diagnostic code for CeD used as proxy). Case definition 2 was defined as the first ever positive tTG-IgA test followed by biopsy-confirmed CeD. The prevalence of diagnosed CeD was estimated for each study year from 2013 to 2022. Prevalence estimations were age- and sex-standardized using 2022 US Census data.

Results

The total population (denominator) comprised ~81 million individuals; of whom, 110,140 had ≥ 1 inpatient or ≥ 2 outpatient diagnostic codes for CeD, 41,184 had ≥ 1 positive tTG-IgA test and 44,641 had biopsy-confirmed CeD. Among all individuals that were tested for tTG2-IgA, 0.85% (95% confidence interval [CI]: 0.82, 0.89) were positive for CeD. The age- and sex-standardized prevalence of diagnosed CeD according to case definition 1 modestly increased from 0.27% (95% CI: 0.27, 0.27) in 2013 to 0.35% (0.34, 0.35) in 2022. Over the same time period, the age- and sex-standardized prevalence of diagnosed CeD according to case definition 2 increased from 0.01% (0.01, 0.01) to 0.03% (0.03, 0.03), respectively.

Conclusion

The overall prevalence of diagnosed CeD in the USA modestly increased from 2013 to 2022. During this same time period, the proportion of patients who underwent an EGD after a positive tTG-IgA test steadily rose. Validation of the CeD case definitions used in this study will be important to enable these results to be replicated or refuted. Furthermore, a standardized and validated CeD case definition will support comparisons between studies and inform better clinical care/disease management.

Disclosure

MA, SM, NC, KG and DAL are employees of Takeda Development Center Americas, Inc. and receive stock or stock options.

Introduction

The early diagnosis of pancreatic cancer has long been considered a major clinical challenge. Recently in Japan, imaging-based screening strategies focusing on indirect findings have ushered in a new era, enabling the detection of carcinoma in situ and high-grade pancreatic intraepithelial neoplasia (PanIN). This study aimed to elucidate the molecular evolutionary mechanisms of PanIN development and progression.

Aims & Methods

We conducted detailed histopathological analysis and multi-regional genomic sequencing on 33 lesions obtained from a single patient with a family history of pancreatic cancer. The patient initially underwent distal pancreatectomy for a branch duct-type intraductal papillary mucinous neoplasm (IPMN) accompanied by adjacent main pancreatic duct (MPD) stenosis, followed by remnant pancreatectomy four years later due to newly detected ductal irregularities. The analyzed lesions included 15 low-grade PanINs, 14 high-grade PanINs, two low-grade IPMNs, and two concomitant pancreatic ductal adenocarcinoma components. Molecular analyses included KRAS and GNAS mutation detection using droplet digital PCR, targeted sequencing using a pancreatic cancer-related gene panel, and whole-exome sequencing. Tumor phenotypes were assessed by immunohistochemistry.

Results

Among numerous low-grade PanINs harboring various KRAS mutations, four distinct multicentric high-grade PanINs arose in the pancreatic body and tail. These included a laterally spreading high-grade PanIN within the stenotic MPD, characterized by KRAS G12D, TP53 deletion, and GATA6 Y83TfsX54; and three discrete high-grade PanINs located in branch ducts, all harboring KRAS G12V accompanied respectively by TP53 Y107D; TP53 S241F and ARID1A Q386X and S2096X; and TP53 G245S and ARID1A Q1066X. A low-grade gastric-type IPMN harboring KRAS G12R was determined to be clonally independent from the adjacent high-grade PanINs. A low-grade PanIN with KRAS G12D was identified at the pancreatic cut margin, though it showed no evidence of malignancy. In the remnant pancreatic head, a high-grade PanIN harboring KRAS G12D, TP53 deletion, and GATA6 Y83TfsX54—identical to the dominant clone in the pancreatic body—had extended along the MPD from the ductal stump to the ampulla. Two small invasive carcinoma foci were found to be continuous with this high-grade PanIN and shared identical KRAS, TP53, and GATA6 mutations, along with additional copy number variations affecting several genes. Another small high-grade PanIN with KRAS G12D and TP53 C275Y was identified in a neighboring branch duct. Furthermore, a germline CDKN2A H66R variant was detected, suggesting a potential hereditary predisposition to pancreatic tumorigenesis. The patient has remained recurrence-free for four years following the remnant pancreatectomy.

Conclusion

In high-risk individuals with a family history of pancreatic cancer or IPMN, PanINs may develop in large numbers, and multiple carcinomas in situ can arise simultaneously. Among these, clones exhibiting pronounced intraductal proliferation or progression toward invasion—thereby impacting clinical outcomes—may be selectively favored. This study provides novel insights into the clonal selection and molecular progression of multicentric high-grade PanINs. To our knowledge, this is the first report to comprehensively delineate the molecular trajectory of multifocal high-grade PanINs in a high-risk patient.

Introduction

The rise in obesity rates has triggered a surge in associated health issues, with metabolic syndrome (MS) affecting approximately 25% of populations in Western countries. Severe acute pancreatitis (AP) is associated with mortality rates as high as 50%. Prior research has linked components of MS to heightened complications and mortality in cases of AP.

Aims & Methods

This meta-analysis aims to elucidate potential risk factors and their combined effects on the outcomes of AP. We performed a systematic search of PubMed, Embase, and the Cochrane Library until November 1, 2023, identifying studies based on specified criteria. We investigated the influence of MS and its components (obesity, hypertension, diabetes mellitus, and hypertriglyceridemia) on AP outcomes, calculating pooled odds ratios (OR) with 95% confidence intervals (CIs). The study protocol was registered with PROSPERO under the identifier CRD42023471092.

Results

From an initial 15,904 records, 93 studies were included in the analysis. Overweight and obesity emerged as significant risk factors for complications (local OR: 2.677, 95%CI: 1.421-5.044; systemic OR: 2.404, 95%CI: 1.481-3.901) and the severity of AP (BMI≥30 kg/m², OR: 3.058, 95%CI: 1.369-6.829). Elevated triglyceride levels were linked to ICU admissions (OR: 2.546, 95%CI: 1.529-4.237) and severe AP (OR: 2.372, 95%CI: 1.275-4.413); hypertension correlated with increased mortality (OR: 2.135, 95%CI: 1.870-2.437), while diabetes was associated with higher odds of ICU admission (OR: 1.645, 95%CI: 1.358-1.992) and severe AP (OR: 1.49, 95%CI: 1.09-2.03). Our findings suggest that MS may elevate the likelihood of severe AP (OR=1.398, 95%CI: 0.918-2.129).

Conclusion

The individual components of metabolic syndrome are significant risk factors for complications, severity, and mortality related to acute pancreatitis. It is imperative to prioritize lifestyle counseling, education, and effective management for patients dealing with obesity.

Clinical Case Summary

A 71-year-old female presented to the gastroenterology clinic following a two year history of dysphagia and sensation of food sticking in the oesophagus. Her dysphagia was limited to solid foods, and symptoms were not exacerbated by positional change. Pain was mostly localised around the sternal notch where she would have the sensation of a food bolus. Over the preceding 2 years, she had experienced about 7.5kg of weight loss with no constitutional symptoms of fevers or fatigue. Her past medical history included hypertension, dyslipidaemia, lower back pain, cold agglutinin disease, monoclonal B lymphocytosis and peripheral arterial disease. On examination, there were no signs of malnourishment or palpable lymph nodes in the axilla, neck or supraclavicular region. Her abdomen was soft and non-tender. Given largely non-illuminating blood results, an oesophageal-gastroduedonoscopy was performed. However, no findings were noted, specifically no oesophageal webs, Zenker diverticulum, gastroparesis, trachealisation of the oesophagus or corrosive pathology. H. pylori was also not isolated on histopathology. A barium swallow was then performed which showed extensive external compression of the proximal third of the oesophagus at the level of the arch of the aorta, most indicative of dysphagia lusoria (Fig 1). Computed tomography angiography (CTA) showed retroesophageal aberrant right subclavian artery bifurcating from the ascending aorta independent of a brachiocephalic artery and causing external oesophageal compression (Fig 2 & 3). Given this definitive diagnosis, the patient was then seen in clinic where management of dysphagia lusoria was explained. Despite ongoing symptoms, the patient decided to continue with conservative management and lifestyle modifications, which included eating smaller bites and increase in fluid intake. Although an extensive compression typically requires surgical intervention, our patient was stable at two-year follow-up (Fig 4 A-B).

References

Figure 1: Barium swallow examination showing extrinsic compression of the proximal third of the oesophagus at the level of the aortic arch (white arrow).
Figure 2: Axial view of computed tomography angiography (CTA) showing the posterior course of the retroesophageal aberrant right subclavian artery.
Figure 3: Axial view of computed tomography angiography (CTA) showing compression of oesophagus (white arrow) by the retroesophageal aberrant right subclavian artery (white arrowhead).
Figure 4: Computed tomography angiography (CTA) multi-planar reconstruction (MPR) showing the posterior course of the right subclavian artery (white arrow), crossing the mediastinum and compressing the oesophagus. A. coronal view B. Sagittal view

Disclosure

None.

Introduction

The PAN-PROMISE symptom score is the first patient-reported outcome (PROM) in acute pancreatitis (AP), and it was developed and validated in a prospective cohort of patients to be used as an endpoint in research. The aim of this study was to assess the performance of the score in a large randomized controlled trial (RCT) and its association with well-established AP endpoints.

Aims & Methods

This is an ancillary study of the WATERFALL trial, where PAN-PROMISE was evaluated at baseline, 24, 48 and 72 hours. The study examined the association between PAN-PROMISE with stablished endpoints in AP: severity, pancreatic and/or peripancreatic fat necrosis (necrosis), infected necrosis, intensive care unit (ICU) admission, persistent organ failure (POF), prolonged hospital stay and mortality. Areas under the ROC curve (AUC) were calculated and used to compare baseline PAN-PROMISE and baseline Bedside Index for Severity in AP (BISAP) for the prediction of these endpoints.

Results

248 patients from the WATERFALL trial were included. A statistically significant association was found between PAN-PROMISE and severity, necrosis, POF, ICU admission, and prolonged hospital stay at all checkpoints (p<0.05). Higher scores were also significantly associated with infected pancreatic necrosis at 24, 48, and 72h and death at baseline and 24 hours. PAN-PROMISE baseline score had a higher AUC than BISAP for severity and necrosis, but the results were not statistically significant.

Conclusion

In the context of a RCT, the PAN-PROMISE score, a patient-centered measure, has been validated with established AP outcomes and as an endpoint for future clinical trials.

Introduction

​Pancreatic fibrosis (PF), a pathological hallmark of chronic pancreatitis, serves as a critical mediator in the progression of numerous pancreatic disorders. Early identification of fibrotic changes presents a strategic opportunity to intervene in disease pathways, potentially curbing the advancement of pancreatic pathologies. It makes research of non-invasive radiological PF assessment perspective.

Aims & Methods

Aim of our study was to evaluate the possibility of multidetector computed tomography (MDCT) post-processing parameters in PF grade assessment.
Methods. Results of contrast-enhanced 128-row MDCT from 165 patients (mean age 57.9±13.5) who underwent surgery from April 2022 to February 2024 due to pancreatic tumors and advanced chronic pancreatitis were analyzed. We calculated contrast enhancement ratio (CR) between venous phase (VP) and non-contrast MDCT, and normalized CR (NCR) during the pancreatic phase (PP) and VP, also we measured pancreas attenuation during MDCT examination. PF morphological grade was assessed according to Klöppel & Maillet’s scoring system [1] and scaled into three grades: mild, moderate and severe PF.
This study was conducted within the healthcare research project “Assessment of pancreatic fibrosis as a prognostic factor for its diseases course” funded by Autonomous non-profit organization "Moscow Center for Innovative Technologies in Healthcare" administered by the Moscow Healthcare Department.

Results

The values of post-processing CT results were compared in groups with different degrees of PF. Mean CR were significantly higher (p=0.001) in patients with severe PF (CR 1.16±0.65 HU) than in patients with mild PF (CR 0.78±0.31 HU). CR significant increase (p=0.03) was found in patients with signs of inflammatory changes in the pancreas tissue (CR 1.14±0.6 HU) than in those without them (CR 0.81±0.3 HU). There were no significant differences between the NCRPP and NCRVP, and the degree of PF, which we had shown in publications of our preliminary results. We suppose the main reason of this fact is study groups enlargement as well as measurement technique improvement, led to results clarification.

Conclusion

The CR value increased in patients with severe degree of PF and decreased in patients with mild PF. Also, there was a significant relation between CR increase and presence of early signs of pancreatic inflammatory changes. Thus, there was a relationship between MDCT postprocessing results and morphological signs of PF, which can be used for pancreatic fibrosis non-invasive diagnosis and identification of additional signs of early chronic pancreatitis.

References

1. Esposito I, Hruban RH, Verbeke C, et al. Guidelines on the histopathology of chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and the European Pancreatic Club. Pancreatology. 2020;20(4):586-593. doi:10.1016/j.pan.2020.04.009