Introduction

Methods to clear CBDS carry varying risk of adverse effects while leaving them in situ can lead to complications secondary to retained stones.^1–3 Thus, the modality of choice reasonably affects the assessment of whether an attempted removal of asymptomatic CBDS is feasible and adequate. In Sweden, available methods to clear common bile duct stones identified on intraoperative cholangiography during cholecystectomy are flushing/manipulating with cholangio catheter, trans cystic stone extraction, intra-operative endoscopic retrograde cholangiopancreatography (IOERCP), postoperative ERCP, laparoscopic choledochotomy, open choledochotomy and leaving the stone in situ.

Aims & Methods

This observational cohort study was based on the national Swedish Register for Gallstone Surgery and ERCP (GallRiks) with validated prospectively assembled data for 90% of all cholecystectomies and ERCP procedures in Sweden from 2009 to 2023.⁴ The aim was to assess efficacy and safety of the respective methods of clearing CBDS by estimating their odds ratio (OR) of failing to reach textbook outcome. Leaving CBDS in situ was considered reference method.
Textbook outcome was defined as cholecystectomy and CBDS clearance laparoscopically completed in one session without immediate or 30-day surgical complications (bleeding from wound or GI tract, wound dehiscence, wound infection, sepsis, bile duct injury with or without leakage or bleeding), readmissions, reinterventions, stent placement or prolonged postoperative hospitalization beyond three days.
The size of CBDS was categorized as small (<4mm) intermediate (4-8 mm) and large (>8mm). Patients were considered asymptomatic if no previous or current sign of bilirubinemia, cholangitis or pancreatits was recorded.

Results

Among the 192 203 patients in the register between 2009 and 2023, 25 295 patients presented with a CBDS during cholecystectomy. Failure to achieve textbook outcome was seen for 12 147 (48%) across all stone sizes and management options. Odds ratio of failing textbook outcome when adjusting only for CBDS size was 0.7 (95%CI 0.63-0.77) for intraoperative ERCP and 0.63 (95% CI 0.55-0.71) for transcystic extraction while flushing and manipulating the stone had OR 0.5 (95% CI 0.44-0.57). Laparoscopic choledochotomy had OR 14.36 (95% CI 8.83- 25.09) to fail textbook outcome. All compared to leaving the stone in situ.
For a subgroup of asymptomatic stones smaller than 4mm the flushing manipulating option was the only one beneficial compared to leaving them in situ with unadjusted OR 0.73(95% CI 0.59-0.90) of failing textbook outcome.

Conclusion

This study introduces a novel composite outcome measure—textbook outcome—to define successful, complication-free clearance of common bile duct stones (CBDS) encountered during cholecystectomy. Using this measure, the greatest benefit was seen in the flush/manipulate group, which was also the only approach that provided a clear advantage for small asymptomatic stones compared to leaving them in situ.
Balancing safety and efficacy of CBDS clearance methods remains essential, given the potential for complications associated with interventions in the common bile duct.
Importantly, small asymptomatic stones did not seem to benefit from more invasive removal techniques beyond flushing and manipulation with the cholangiocatheter,
when evaluated using this composite outcome measure. However, these results need to be interpreted with caution due to the risk of selection bias.

References

1 Lammert F, Gurusamy K, Ko CW, Miquel J-F, Méndez-Sánchez N, Portincasa P, et al. Gallstones. Nat Rev Dis Primers [Internet]. Nature Publishing Group; 2016 Apr 28 [cited 2023 Nov 6]; 2: 1–17. Available from: https://www.nature.com/articles/nrdp201624
2 Saito H, Kadono Y, Shono T, Kamikawa K, Urata A, Nasu J, et al. Remaining issues of recommended management in current guidelines for asymptomatic common bile duct stones. World J Gastroenterol [Internet]. 2021 May 14 [cited 2023 Oct 24]; 27: 2131–2140. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117734/
3 Berg LS, Friis-Andersen H, Zinther NB, Öztoprak M, Gotschalck KA. Feasibility and outcome of transcystic laparoscopic common bile duct exploration as first-line treatment for common bile duct stones: a retrospective cross-sectional study. Surg Endosc [Internet]. 2025 Feb 11 [cited 2025 Feb 17]; 1–11. Available from: https://link.springer.com/article/10.1007/s00464-025-11587-7
4 Enochsson, L. S G. GallRiks Annual Reports 2018 [Internet]. 2019 [cited 2019 Oct 3]. Available from: https://www.ucr.uu.se/gallriks/fou/arsrapporter/arsrapport-2018-2/viewdocument/837

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

Genetic variants associated to a higher risk of developing eosinophilic esophagitis (EoE) and other atopic conditions have been described. However, no study has investigated how these genetic variants influence clinical features of EoE or the atopic concomitances that usually accompanied this disease.

Aims & Methods

This study aims to assess whether single nucleotide polymorphisms (SNPs) in genes related to EoE and atopies associate with disease features and atopic concomitances in a large, representative cohort. Patients diagnosed of EoE according to clinical guidelines were recruited from 4 Spanish referral hospitals and demographical and clinical data were obtained both retrospectively and prospectively. The concomitant atopies analyzed were rhinitis, conjunctivitis, asthma, dermatitis and any food allergy. The recruited cohort was randomly divided into discovery (DC) and validation cohorts (VC) (70% and 30%, respectively). Genotyping was performed using an Open Array platform with 60 SNPs on DNA obtained from peripheral blood. Chi-square or Fisher’s exact test were used for statistical comparisons.

Results

Overall, 647 patients (74.7% male, 32.4±15.2 mean age) were included; 81% of them with an inflammatory phenotype. Rhinitis was the most common atopy (55.8%), while dermatitis was the least frequent (17.5%). Food allergy was documented in 28% of patients.
In relation to EoE characteristics, four SNPs were initially associated with endoscopic findings (measured by EREFS score) and with peak eosinophil counts in esophageal biopsies within the discovery cohort. However, only rs77569859 in the CAPN14 gene remained statistically significant in the validation cohort. TC and CC genotypes of this variant, present in 23.7% of the cohort, were associated with lower EREFS score under a dominant model (3.30±1.60 vs 2.92±1.66, p=0.011 DC/0.002 VC). Additionally, rs76562819, also in CAPN14 gene, showed a trend toward a lower peak eosinophil count per high power field (47.7±24.4 vs 66.6±48.3, p=0.005 DC/0.116VC) under a recessive model (AG and GG genotypes in 11.3% of our patients).
Regarding atopic comorbidities, rs1800925-TT in IL13 (found in 5.7% of our patients) was associated a higher prevalence of conjunctivitis (60% vs 39% in the overall cohort, p=0.020 DC/0.057 VC) and showed a trend toward increased asthma prevalence (54% vs 35%, p=0.056 DC/0.155 VC). A weaker association with asthma was observed for STAT6 rs324015, with an increased prevalence in patients with AG and GG genotypes (41% vs 32%, p=0.079 DC/0.162 VC; present in 34.9 % of the cohort). For dermatitis, a protective effect was seen in patients with the TT genotype of rs2032582 in ABCB1 gene (found in 16.1% of our patients), as the prevalence decreased from 19% to 8% (p=0.033 DC/0.157 VC). No consistent associations were found for rhinitis or food allergy with any SNP across both cohorts.

Conclusion

We have identified significant associations between genetic variants and both clinical features and atopic comorbidities in Spanish patients with EoE, highlighting the potential of genetic profiling to improve clinical characterization and patient management.

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