Introduction

As a chronic condition, eosinophilic oesophagitis (EoE) requires lifelong therapeutic management and multidisciplinary care. Reports suggest clinicians managing EoE have gaps in knowledge and competence, which may lead to suboptimal patient outcomes. We aimed to assess whether a purpose-specific curriculum comprising a series of continuing medical education (CME) activities addressed these gaps.

Aims & Methods

Four faculty-led, CME-accredited activities on EoE were hosted on two free-to-access online medical education websites. Each activity provided 30–60 minutes of education in short videos and addressed learning objectives based on a review of published literature and expert insights. Educational outcomes were assessed using Moore’s expanded outcomes framework Levels 1–4 (participation, satisfaction, knowledge, and competence, respectively). Intent to change practice and need for further education were also assessed. Level 1 data were captured using Google Analytics; Level 2–4 data were captured using pre- and post-activity questionnaires administered by an independent third party and analysed by the authors. Across the curriculum 21,032 participants engaged with the content, with a sample size of 800 available for the Level 2–4 analysis; the margin of error was calculated as ~3% based on a standard confidence interval of 95%.

Results

Within 12 weeks of launch, a mean of 5,258 participants engaged with each curriculum activity (Moore’s Level 1). Mean satisfaction (Moore’s Level 2) was high (87.3%) across the curriculum. From baseline to follow-up, significant average increases in declarative knowledge (24%, p=0.012), procedural knowledge (18%, p<0.001), and competence (16%, p=0.004) were observed (Moore’s Levels 3a, 3b, and 4, respectively) (Table). Gastroenterologists had the highest proportion of correct answers at follow-up across all activities (86–95%). Allergists/immunologists had the largest increase in knowledge from baseline to follow-up (51%, activity 1); the smallest increase was seen for gastroenterologists (7%, activity 2). For all specialities, the lowest proportion of correct answers at follow-up was for questions on pathophysiology/causes of EoE (Table). Overall, 64% of learners would change their practice following participation in ≥1 curriculum activity and ~20% indicated further education would be beneficial.

Conclusion

This expert-led, CME curriculum led to significant improvements in clinician knowledge and competence surrounding the latest research and best practices in the pathophysiology, diagnosis, and management of EoE, which may lead to improvements in patient care and outcomes. Findings support further development of online, multiformat educational activities to address clinical knowledge and competence gaps. Future programs should focus on the underlying pathophysiology of EoE and how this may inform practice.

References

None

Disclosure

Stuart Carr discloses: Consulting fees/advisory board: Sanofi. Honoraria (speakers bureau): Sanofi, Biologix.
Evan S. Dellon discloses: Research funding: Adare/Ellodi, Allakos, Arena, AstraZeneca, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, Shire/Takeda. Consultant: Abbott, Abbvie, Adare/ Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Landos, LucidDx, Morphic, Nexstone Immunology, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, Upstream Bio. Educational grant: Allakos, Holoclara, Invea
Nirmala Gonsalves discloses: Consultant: Allakos, Astra-Zeneca, Regeneron-Sanofi, BMS, Knopp. Speaking: Regeneron-Sanofi. Royalties: Up To Date.
Salvatore Oliva discloses: Consulting fees from Sanofi.
Jonathan M. Spergel discloses: Consultant: Regeneron and Sanofi-Genzyme, Novartis, Allakos. Grants/Research Support: NIH, FARE, Regeneron, Novartis, Sanofi, Celgene. Speaker’s Bureau: Medscape.
Mário C. Vieira: No conflicts of interest associated with the submitted work to declare.
Katie Bickford, Kathy Day, Alex Noble, Anne Nunn and Alison Scott: No financial relationships to disclose.

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

Radiofrequency ablation is considered the standard therapy for flat dysplastic BE. Hybrid APC is a newer under evaluation, less expensive technique, but with the need of a special injection device and catheter. Aim of the study: To evaluate the efficacy of a standard APC catheter after submucosal injection for BE ablation.

Aims & Methods

To evaluate the efficacy of a standard APC catheter after submucosal injection for BE ablation. Naïve or after previous treatments patients with BE and low - grade dysplasia (LGD) were prospectively evaluated. Sodium chloride solution 0.9% was injected submucosally with a 23 G needle followed by APC application with a standard catheter (ERBE APC 300, 45Watts) on the created cushion. The same procedure was repeated for most of BE surface to be cauterized, with special attention not to ablate large circumferential areas. Patients were under high dose PPIs. Biopsies were taken according to the Seattle protocol during the follow-up.

Results

31 patients, 28 males (90.3%), 56.7±12.5 years old. Their initial diagnosis was: 19 patients with LGD (61.3%), 7 with high grade dysplasia (22.6%), and 5 with intramucosal cancer (16.1%). Eleven patients (35.5%) had previous endoscopic mucosal resection (EMR) while 7 (22.6%) had received radiofrequency ablation (RFA). Median BE length with LGD at the beginning of APC was 4cm (25th-75th:2-7, min-max:1-10). Median follow-up:10.1(1-108) months. In total 20 (64.5%) patients completely eradicated BE. For the remaining 11 patients APC led to a substantial reduction of BE length [Initial Median: C3M6 (Min: C0M1, Max: C6M8) to a final median: C0M2 (Min:C0M1, Max:C2M5] but the study is ongoing. Initial BE length was correlated to APC sessions needed (r= 0.54, p<0.01) but was not a limiting factor for complete BE eradication. Instead, smoking was an aggravating factor for BE complete eradication (HR=3.12, 95%CI.: 1.2-8.12, p=0.02). No death, hospitalization, severe hemorrhage, or perforation were observed. In 7 patients moderate pain requiring paracetamol, resolved after a few hours of in hospital supervision while 11 patients had mild dysphagia the following days without permanent stenosis.

Conclusion

Conclusions: 1) Standard APC after submucosal injection is safe and tolerable for BE ablation. 2) It may be applied in naïve patients or if other techniques were previously used. 3) Length increases the number of sessions needed but does not seem to be a limiting factor for APC application.

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

Endoscopic ultrasound (EUS) is an important tool for the evaluation of patients with common bile duct (CBD) dilation without obvious identified aetiology after ultrasonography (US), computed tomography (CT) and/or magnetic resonance cholangiopancreatography (MRCP).

Aims & Methods

The aim of this study was to evaluate the diagnostic performance of EUS for CBD dilation in patients with a negative initial study.
Retrospective, unicentric and cohort study including patients who underwent EUS for CBD dilation (diameter ≥7mm if intact anatomy or ≥10mm if prior cholecystectomy) in the absence of obvious pathology on prior imaging, including US, CT and/or MRCP, from January 2016 until June 2022. All EUS procedures were performed with a linear echoendoscope.

Results

Totally, 109 patients were included, 50 patients without symptoms or altered liver biochemistry (45.9%). Among the 41 patients with positive EUS, 33 patients had choledocholithiasis (30.3%), 6 chronic pancreatitis (5.5%) and 2 had ampullary cancer (1.8%). Older age was associated with positive EUS (median 79 vs 71 years, p=0.030). Patients with jaundice, cholelithiasis and altered liver biochemistry were 16.2 (p=0.002), 3.1 (p=0.024) and 2.9 (p=0.009) times more likely to have positive EUS, respectively.
A total of 53 patients underwent MRCP with a negative result (48.6%). In this group, 12 patients had a positive EUS, 10 had choledocholithiasis (18.9%) and 2 had chronic pancreatitis (3.8%). Of those, patients with abdominal pain and jaundice were 15.4 (p<0.001) and 20.0 (p=0.007) times more likely to have positive EUS, respectively. CBD diameter in MRCP was not associated with finding a causative lesion (p=0.473).
Considering only asymptomatic patients without altered liver biochemistry, CBD diameter ≥8.5mm, evaluated by CT, had a sensibility of 100% and specificity of 75% in predicting a positive EUS (AUC 0.734, p=0.048).

Conclusion

EUS is a useful diagnostic method for patients with unexplained CBD dilation, with a higher yield, even in patients with negative MRCP, and especially in patients with older age, symptoms such as abdominal pain and jaundice, cholelithiasis and/or altered liver biochemistry. CBD diameter evaluated by CT had a moderate discriminative ability in predicting a positive EUS in asymptomatic patients without altered liver biochemistry.

Introduction

In recent years, the number of early-onset CRC (EO-CRC) diagnosed at the age of less than 50 years has been increasing. Previous studies suggest that EO-CRC may have higher malignant potentials and a worse prognosis than late-onset CRC. However, the reason why EO-CRC is regarded as aggressive cancer and result in delayed diagnosis remains unclear. We thought that both the lack of appropriate opportunities for screening or medical examination and the bias that was caused owing to being analyzed altogether regarding the different clinical stages could affect worse prognosis of EO-CRC. In this study, we focused on T1 cancer to highlight the essential features of EO-CRC to minimize the bias caused by the time of diagnosis.

Aims & Methods

This study is a secondary analysis of the main JSCCR (The Japanese Society for Cancer of the Colon and Rectum) project, “International joint research on lymph node metastasis in CRC”. Utilizing 4673 T1 CRC cases treated between July 2009 and December 2016 at 27 facilities belonging to JSCCR, we divided the patients into 5 groups according to age at the diagnosis: 49 years or younger, 50‒59 years, 60‒69 years, 70‒79 years, and 80 years or older. To analyze the clinicopathological features including sex, tumor location, macroscopic type, tumor size, histology, submucosal invasion depth, lymphatic/venous invasion, tumor budding, lymph node metastasis, and treatment methods, the Spearman’s correlation test was used. The difference of disease-free survival (DFS) between early-onset and later-onset CRC was also examined using log-rank test and Kaplan–Meier method.

Results

The cases of EO-CRC were 349 (7.5%). Among age groups, the proportion of rectum (from 49 years or younger to 80 years or older;44.1%, 42.0%, 36.6%, 29.0%, and 12.0%, respectively; P <0.05), protruded type (62.2%, 59.1%, 54.9%, 48.4%, 45.9%; P <0.05), and frequency of lymph node metastasis (10.0%, 7%, 8.0%, 7.0%, 4.6%; P <0.05) were decreased as the age group increased. In terms of sex, the proportion of male tends to decrease as the age group increased (57.9%, 60.8%, 63.5%, 57.0%, 52.7%, respectively; P <0.05). No significant differences were found among the five age groups for tumor size, histology, submucosal invasion depth, vascular invasion, tumor budding, recurrence rate, and treatment. No significant difference was observed regarding DFS between the two groups (5-year DFS; 98.7% for EO-CRC and 94.3% for late-onset CRC).

Conclusion

This study showed that the frequency of lymph node metastasis of T1 CRC decreased according to the increase of age at diagnosis, suggesting that EO-CRC may have a greater biological malignant potential compared to late-onset CRC. As far as we know, this is also the first study to report that “protruded type” would be one of the features of EO-CRC. Although no difference was observed as for DFS between two groups, it was plausible considering that only T1 stage CRC was enrolled in this study. Further studies are warranted to evaluate the clinicopathological features characterizing early stage EO-CRC.

Introduction

Pancreatic adenocarcinoma has a poor prognosis with an overall 5-year survival rate of 10% as most patients present with unresectable or metastatic disease. Evaluation of microsatellite instability (MSI) or deficient DNA mismatch repair (dMMR) status can tailor treatment to increase the efficacy of systematic therapy. However, the adequacy of tissue samples obtained by routine endoscopic ultrasound-guided fine needle biopsy (EUSFNB) of pancreatic adenocarcinoma for MSI/dMMR assessment remains unclear. This study evaluated the role of EUSFNB using the Procore (Cook Medical) biopsy needles for MSI/dMMR assessment. In recent years, a new 20G Procore needle has been developed to overcome the limitations of tissue acquisition of the smaller needles (22G,25G) and the rigidity of the larger one (19G). We also aimed to study the performance assessment between Procore 20G vs 22G needles in tissue acquisition for MSI/dMMR assessment.

Aims & Methods

This was a single-centre study reviewed patients with suspected pancreatic adenocarcinoma who underwent diagnostic EUSFNB in a tertiary referral centre using either 20G or 22G Procore needles from January 2022 to March 2023. The newer 20G Procore needle was designed with a forward side-bevel, whereas the 22G needle had a reverse side-bevel, for tissue core acquisition. Clinical data and characteristics of lesions in all patients undergoing EUSFNB in the participating site are prospectively maintained in a registry for quality control and audit purposes. All cases of adenocarcinoma were tested for MSI/dMMR status by immunochemistry (MLH1, MSH2, MSH6 & PMS2). The primary study outcome measure was the adequacy of tissue samples for MSI/dMMR testing. Secondary outcomes were the rate of histological core tissue acquisition, the difference in the adequacy of tissue for MSI/dMMR testing between 20G and 22G Procore needles and the rate of MSI-high pancreatic adenocarcinoma. The impact of the use of these needles in obtaining adequate tissue on patient management was also evaluated.

Results

A total of 31 patients (mean age 68.2 SD± 8.17; 51% male) with pancreatic adenocarcinoma were included in the study. The mean size for the pancreatic mass was 33.17 SD±20.4 with most of the pancreatic mass located at the pancreatic head, uncinate, and neck region 70% (21/31). The histological yield of EUSFNB was 100%. Overall tissue adequacy rate for MSI/dMMR assessment was 80% (25/31), which was higher with 20G compared to 22G Procore needles (88.8%;16/18 vs 69.2%;9/13, p-value = 0.207). Two of the 23 patients with successful MSI/dMMR testing (8.7%) had MSI-high status. One received second-line treatment with pembrolizumab, and the other received the best supportive care due to worsening liver function and poor functional status.

Conclusion

This study affirmed the feasibility of routine MSI testing from specimens acquired by EUSFNB using the Procore EUSFNB needles. Our results also suggested that the larger 20G Procore needle with forward side-bevel had a higher yield for MSI testing than the 22G needle with reverse side-bevel, even though both needle types could obtain tissue cores for histology, and this should be reassessed by a further study with larger sample size that is adequately powered.

Disclosure

None