Introduction

The risk of post-resection colorectal stricture significantly increases when more than 90% of the circumference is affected.

Aims & Methods

In this study, we aimed to evaluate post-resectional stricture incidence and predictive factors in patients undergoing colorectal ESD for whole circumferential lesions. We retrospectively analysed a prospectively maintained dataset of patients undergoing ESD for colorectal lesions involving≥90% of the luminal circumference at 27 tertiary referral centres across Europe, North Africa, Asia, and North America between June 2018 and September 2024. Baseline clinical data and procedural outcomes, including effectiveness, safety and stricture development were collected. The primary endpoint was to evaluate the incidence and predictive factors of post-resectional strictures after circumferential ESD.

Results

Overall, 301 patients were included in the analysis [median age: 71 (IQR: 62-79); female sex: 175 (58.1%)] 254 (84.4%) lesions were from the rectum, 47 (15.6%) were colonic, showing a median long-axis of 95 (70.5-130) mm. 100% circumferential involvement was present in 97 (63.8%) cases. Among those, one case was aborted due to technical issues (99.7% technical success). The median procedure time was 184 (IQR:133.5-270) minutes. R0 and oncological curative resection rates were 81.7% and 80.3%, respectively. Histopathological diagnosis showed the presence of adenocarcinoma in 107 (35.7%) cases. In 29 (9.7%) cases, patients underwent surgery either due to delayed perforation (2/29, 6.9%) or invasive adenocarcinoma (27/29, 93.1%). Consistently, 271 lesions were available for stricture assessment. 92/271 (33.9%) patients developed stricture, with 84/92 (91.3%) reporting symptoms after a median time of 31 (IQR:21-72) days. Most cases (87/92, 94.6%) were in the rectum, while a few belonged to the colon (5/43, 5.4%) (p<0.001). Strictures needed treatment in 87/92 (94.5%), either with endoscopic balloon dilation (65/92, 62.1%), bougie dilation (23/92, 26.4%) or other methods, such as home self-dilation (6/92, 6.5%), self-expandable metals stents (SEMs) placement (1/92, 1.1%), lumen apposing metal stents (LAMs) (2/92, 2.3%) or incisional therapy (4/92, 4.6%). All cases were successfully managed. Risk factors for rectal stricture development were a higher median long-axis of the specimen (p<0.001), 100% circumferential involvement (p<0.001), the whole rectum (p=0.02) and the oral side rectal (p=0.02) location. At multivariate analysis, the 100% circumferential involvement and higher long-axis confirmed to be risk factors, showing an odd ratio of 3.38 (CIs 1.77-6.08) and 1.01 (CIs 1.01-1.20), respectively.

Conclusion

Circumferential ESD for colorectal lesions involving≥90% of the circumference is a feasible technique, showing a high rate of stricture development, which can be effectively treated through endoscopy. Leaving a small island of normal mucosa within the resection (especially when there is a long axis) could be an effective strategy to prevent stricture development.

Introduction

Eosinophilic esophagitis (EoE) is type-2 chronic inflammatory disorder usually accompanied by other atopic conditions including rhinitis, conjunctivitis, bronchial asthma, dermatitis, hives or chronic rhinosinusitis with nasal polyps. The influence of these atopies in the response to the EoE therapy has been barely investigated, with opposite results in small cohorts (1,2).

Aims & Methods

We aim to describe atopic concomitances in European EoE patients and to evaluate its influence on effectiveness of first-line therapy, consisting in proton-pump inhibitors (PPIs), swallowed topical corticosteroids (STCs) and food-elimination diets (FEDs).
A cross-sectional analysis of the multicenter EoE CONNECT registry (3) was performed. Demographic and clinical data from patients recruited at 42 hospitals in 4 European countries were extracted on March 25^th, 2025. Concomitant atopies were classified as seasonal or persistent. Clinico-histological response (CHR) was defined as the simultaneous presence of symptomatic remission and a peak eosinophil count <15 eosinophils per high power field after therapy.

Results

Overall, 3,900 patients (75.6% males, mean age 33.3 ±15.1 years) were analyzed (Table). CHR rate after first-line monotherapy with PPIs, STCs or FEDs was 50.4% (n=2,685). PPIs was the only treatment affected by concomitant atopy: presence of asthma and hives significantly reduced CHR rates to PPIs (42.7% vs 49.7%, p=0.005, and 39.3% vs 48%, p=0.044, respectively), and CHR also tended to be lower in presence of conjunctivitis (43.6% vs 48.4, p=0.067) and dermatitis (43.2% vs 48.3%, p=0.081). Seasonal or persistent presentation of atopy did not influence response to treatment. Taking into account age at diagnosis, the effect of concomitant atopy in reducing CHR to PPIs was exclusively observed in adults (≥18 years old) for asthma (43.8% vs 51.3%, p=0.007) and dermatitis (42.6% vs 50.3%, p=0.026), and in children (<18 years old) for hives (17.4% vs 39.9%, p=0.032).
We next analyzed whether the number of concomitant atopies influenced CHR to first-line therapy. While no differences were found among patients who presented only one atopic condition, the presence of 2 or more atopies reduced PPI effectiveness in adults (45.0% vs 50.7%, p=0.032) and to FEDs in children (23.5% vs 59.3%, p=0.020). A reduction in CHR rate after PPI therapy was even greater in adults with 3 or more atopies concomitant to EoE (39.0% vs 50.4%, p=0.001). Effectiveness of first-line STCs were not affected in any of these comparisons.

Conclusion

The coexistence of asthma, dermatitis and hives determined lower response to PPI therapy for EoE. Association of 2 or more atopic condition further decreased effectiveness of PPIs in adults and of FEDs in children.

References

1. Ancellin M, Ricolfi-Waligova L, Clerc-Urmès I, et al. Management of eosinophilic esophagitis in children according to atopic status: a retrospective cohort in northeast of France. Arch Pediatr. 2020;27(3):122-127.
2. Reed WD, Ocampo AA, Xue Z, et al. Eosinophilic esophagitis patients with multiple atopic conditions: clinical characteristics and treatment response to topical steroids. Ann Allergy Asthma Immunol. 2023;131(1): 109-115.e2.
3. Lucendo AJ, Santander C, Savarino E, et al. EoE CONNECT, the European Registry of Clinical, Environmental, and Genetic Determinants in Eosinophilic Esophagitis: rationale, design, and study protocol of a large-scale epidemiological study in Europe. Therap Adv Gastroenterol. 2022;15:17562848221074204.

Introduction

Endoscopic Submucosal Dissection (ESD) is the best endoscopic technique that enables en bloc resection of superficial colorectal neoplasms.Despite its effectiveness, ESD is not very widespread in Western countries due to technical complexity, long procedure times, and a steep learning curve. These barriers have created a significant gap in adoption and outcomes between Eastern and Western centers. Underwater ESD (U-ESD) has been introduced to simplify the procedure. This study aimed to evaluate the effectiveness of U-ESD versus conventional gas-based ESD (G-ESD) in a Western center, focusing on procedural efficiency and safety.

Aims & Methods

This is a single-center, prospective randomized controlled trial conducted at Fondazione Campus Bio-Medico in Rome between December 2024 and April 2025.Forty patients with non-pedunculated colorectal lesions were randomly assigned in a 1:1 ratio to undergo either Underwater ESD (U-ESD) or conventional ESD with insufflation of Carbon Dioxide (CO2) (G-ESD).The primary outcome was total procedure time. Secondary outcomes included dissection speed, en bloc and R0 resection rates, use of hemostatic forceps, and the incidence of adverse events such as delayed bleeding, perforation, and post-ESD coagulation syndrome (PECS).

Results

A total of 40 patients referred to our endoscopic unit for ESD between December 2024 and April 2025. The mean size of the colorectal lesions was 57.4 mm and 40.7 mm in the U-ESD and G-ESD groups. The location of the lesions was in the rectum in 15% and 55% of the U-ESD and C-ESD groups, respectively; in the right side of the colon in 35% and 20% of the U-ESD and G-ESD groups, respectively. The morphology of LST was classified as LST-nongranular in 20 % and 25% of the U-ESD and G-ESD groups, respectively; as LST granular in 60% and 35% of the U-ESD and G-ESD groups, respectively. Fibrosis (grade 1 and 2) was present in 45% and 30% of the U-ESD and G-ESD groups, respectively. The mean total procedure time was shorter in the U-ESD group compared with the G-ESD group (53.3 ±33 minutes vs 78.7 ± 25.6 minutes; mean difference,–25.4 minutes; P=0.009).Mean dissection speed was faster in the U-ESD group compared with the G-ESD group (42 ± 26.3 mm2/min vs 13.3 ± 8 mm2/min; mean difference, 28.7 mm2/min; P= 0.001). En bloc and R0 resection rates in both groups were 100%. The use of a hemostatic forceps was significantly lower in U-ESD compared G-ESD (40% vs 90%, P= 0.001). Delayed bleeding occurred in only one patient in G-ESD group and was managed successfully by endoscopic clipping. No perforations occurred in either group. PECS was noted in only one patient in the G-ESD group.

Conclusion

UESD has shown a significantly shorter procedure time and faster dissection speed compared with GESD. These both empower the possibility of considering U-ESD as the preferred colorectal ESD method for colorectal lesions.

Introduction

Pancreatic cancer remains a devastating disease with a poor prognosis, and liquid biopsy utilizing minimally invasive biofluids such as blood and duodenal juice has emerged as a promising approach for early detection. Our group has previously accumulated data on plasma- and duodenal fluid-based liquid biopsy, demonstrating potential clinical utility but also highlighting limitations in diagnostic sensitivity. This study aims to establish a robust cancer diagnostic and risk assessment method using plasma, duodenal juice, and pancreatic juice, while also charactering molecular abnormalities in resected tumors and surrounding tissues. To develop a novel clinical diagnostic framework, we comprehensively evaluated to cancer-associated genetic mutations in biofluids and compared these finding with tissue samples obtained via biopsy or surgical resection.

Aims & Methods

This multi-institutional study, initiated in 2021, focuses on developing a liquid biopsy platform for pancreatic cancer detection. Samples were collected as follows: plasma (n=224), duodenal juice (n=102), and pancreatic juice (n=85). Plasma was collected in 10 mL PAXgene Blood ccfDNA tubes (BD); cell-free DNA (cfDNA) was purified and concentrated to a 30 µL eluate. Duodenal fluid was collected through the endoscopic channel, and pancreatic juice was aspirated directly from the pancreatic duct using a catheter during ERP examination. Both fluid were each mixed with a preservation solution validated in a previous study. Digital PCR (dPCR) was performed to screen for KRAS G12/G13 and A59/Q61 mutations, followed by panel-based sequencing. For this study, we designed a Duplex UMI-based pancreatic cancer gene panel targeting 16 genes, including KRAS, TP53, CDKN2A, and SMAD4, to enable high sensitive detection of tumor-specific mutations.

Results

DPCR screening detected KRAS mutations in 75% of pancreatic juice samples and 50% of duodenal juice samples. Validation of the Duplex UMI-based target sequencing panel in a subset of samples (n=16) demonstrated that a minimum input of 20 ng of liquid-derived, non-genomic DNA was necessary to achieve concordance with mutations identified in matched tissue samples. Inputs below this threshold resulted in significantly reduced coverage and uniformity. Notably, duodenal and pancreatic juice exhibited superior sensitivity, reliably detecting tissue-confirmed mutations down to a minimum variant allele frequency (VAF) of 0.1%. Pancreatic juice not only captured a diverse spectrum of genetic alterations across multiple lesions but also identified mutations absent in corresponding tissue samples, suggesting its potential for detecting subclinical molecular changes. These findings underscore the complementary roles of different biofluids in capturing tumor heterogeneity.

Conclusion

Pancreatic juice-derived DNA shows exceptional promise for the accurate prediction of tumorous lesions, offering a powerful tool to prompt further diagnostic evaluation even in the absence of histological evidence. This approach could substantially enhance early detection and risk stratification in pancreatic cancer. Our ongoing study involves comprehensive analysis of all collected samples using the designed 16-gene panel. These efforts aim to establish liquid biopsy as a central component of pancreatic cancer diagnostics, supporting personalized treatment strategy and improving patient outcomes.

Disclosure

Y.O., K.T. and Y.M. receive funding form Hitachi High-Tech Corporation