Introduction

Gastric outlet obstruction is a common manifestation of advanced gastric, duodenal, and periampullary malignancies, severely affecting quality of life. Endoscopic ultrasonography-guided gastroenterostomy (EUS-GE) may be superior to surgical gastroenterostomy (SGJ) as palliative treatment for this condition, but randomised trials are currently lacking.

Aims & Methods

We performed a multicenter, randomized controlled trial involving palliative patients with a malignant obstruction localized between the pylorus and the distal duodenum, randomizing them 1:1 to either EUS-GE or SGJ. The first co-primary superiority end point was time to solid oral intake. The second co-primary non-inferiority end point was persistent or recurrent obstructive symptoms for which a reintervention was required within six months after treatment. The predefined non-inferiority margin was 20%.

Results

From February 2022 to February 2024, 250 patients were screened in 12 participating hospitals in the Netherlands. Of the 98 enrolled patients, 48 were assigned to EUS-GE and 50 were assigned to SGJ. Median age was 69 versus 70 years and the most prevalent etiology was pancreatic cancer in 58% versus 50% in the EUS-GE group and SGJ group, respectively. Median time to oral intake was significantly shorter in the EUS-GE group compared to the SGJ group: 1 day versus 3 days (hazard ratio, 2.21, 95% CI, 1.43 to 3.42, p=0.0003). In the endoscopic group, 5 patients (10%) experienced persistent or recurrent obstructive symptoms requiring reintervention, compared with 6 patients (12%) in the surgical group (risk difference, 1.6%, upper limit of 90% CI, 8.9%). Clinical success, defined as the ability to tolerate solid oral intake, was higher in the EUS-GE group (96% versus 80%, relative risk, 1.20, 95% CI, 1.03 to 1.39). Median length of hospital stay was shorter in the EUS-GE group (1 day versus 4 days, relative change, 0.46, 95% CI, 0.20 to 0.78). Serious adverse events, defined as Clavien-Dindo ≥3B, were observed in 8% of patients in the EUS-GE group and in 12% of patients in the SGJ group (relative risk, 0.69, 95% CI, 0.21 to 2.31). Median survival was 91 days after EUS-GE (95% CI, 74 to 140) and 74 days (95% CI, 46 to 110) after SGJ. Thirty-day mortality was 13% in the EUS-GE group and 26% in the SGJ group (relative risk, 0.48, 95% CI, 0.20 to 1.14). In the first three months following the procedure, quality of life was not different between the two treatments.

Conclusion

This trial showed that EUS-GE, compared to SGJ, is superior in terms of time to solid oral intake and non-inferior with regards to the rate of persistent or recurrent obstructive symptoms requiring reintervention. Based on these results, EUS-GE should be the preferred palliative treatment for malignant gastric outlet obstruction.

Disclosure

Yorick L. van de Pavert, Janine B. Kastelijn, Marc G. Besselink, Dieke C. Booij, Jurjen J. Boonstra, Judith Boot, Olivier R.C. Busch, Wouter J.M. Derksen, Bas Groot Koerkamp, Akin Inderson, Wim J. Lammers, Daan J. Lips, J. Sven D. Mieog, I. Quintus Molenaar, Alexander A.F.A. Veenhof, Niels G. Venneman, Robert C. Verdonk, Paco M.J. Welsing, Thomas R. de Wijkerslooth, and Hjalmar C. van Santvoort report no conflicts of interest.
Freek Daams is proctor for Intuitive, received educational grants from Medtronic, and received speaker’s fees from Johnson & Johnson and Medtronic.
Paul Fockens is consultant for Cook Endoscopy and Olympus.
Rogier P. Voermans reports research grants from Boston Scientific and Prion Medical, performed as a consultant for Boston Scientific and Cook Medical, and received speaker’s fees from Mylan and Zambon.
Roy L.J. van Wanrooij is a consultant for Boston Scientific.
Marco J. Bruno is a consultant for Boston Scientific, Cook Medical, and Pentax Medical; received support for industry-initiated studies from Boston Scientific and Cook Medical; and received support for investigator-initiated studies from Boston Scientific, Cook Medical, Pentax Medical, Mylan, Interscope, and ChiRhoStim.
Jeanin E. van Hooft received lecture fees from Cook Medical, Boston Scientific, Medtronic, and Abbvie, is an independent observer for Olympus, and is the current secretary general of the federation United European Gastroenterology (UEG).
Leon M.G. Moons is a consultant for Boston Scientific.
Frank P. Vleggaar is a consultant for Boston Scientific.

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.