Introduction

The optimal surgical approach to reduce recurrence rates after laparoscopic repair of paraesophageal hernia (PEH) is yet to be defined. The crural repair is challenged by both axial and transverse-lateral tension, which may compromise durability. The aim of this double-blind randomized clinical trial was to investigate whether a left-sided diaphragmatic relaxing incision in addition to standard crural repair and fundoplication reduces anatomical recurrence rates at one year postoperatively.

Aims & Methods

This study was conducted at two high-volume Swedish centers—Ersta Hospital (Stockholm) and Sahlgrenska University Hospital (Gothenburg)—between August 2019 and August 2023. Adult patients undergoing surgery for PEH were randomized 1:1 to either standard crural repair with total (360°) fundoplication (control) or the same procedure with the addition of a left-sided diaphragmatic relaxing incision covered by synthetic mesh (intervention). Patients with prior hiatal surgery, ASA class IV or above, type I hernia, major esophageal motility disorders, or any contraindication to fundoplication were excluded. Blinding for patients and assessors was maintained throughout follow-up. Pre- and postoperative assessments included computed tomography (CT), symptom questionnaires (Dakkak dysphagia score, Gastrointestinal Symptom Rating Scale [GSRS]), and quality of life (QoL, RAND-36). The primary outcome was radiologically confirmed PEH recurrence at 12 months.

Results

Of 103 patients screened, 76 were randomized (38 per group). Baseline characteristics were well balanced. CT was completed in 72 patients (95%) at 12 months. The recurrence rate was 66% in the control group and 54% in the intervention group (p=0.313). Three patients in the intervention group had asymptomatic CT verified herniation at the site of the diaphragmatic incision. There were no differences in recurrence size distribution (<4 cm vs >4 cm) between groups. Postoperative symptom assessment revealed significant improvements in dysphagia, reflux, indigestion, and abdominal pain in both groups, without intergroup differences. Physical QoL (PCS) improved significantlywhereas mental QoL (MCS) remained unchanged. Two deaths occurred within 90 days postoperatively (1 per group), yielding a 90-day mortality of 2.6%. Other complications included mediastinal abscess (n=1, intervention group) and need for postoperative endoscopic dilatation (n=5 in total). Operation time tended to be longer in the intervention group (150 vs 133 min; p=ns).

Conclusion

In this randomized, double-blind trial, the addition of a left-sided diaphragmatic relaxing incision to standard laparoscopic PEH repair did not improve anatomical recurrence rates, symptom relief or QoL at 12 months after surgery and should not be recommended for routine use. Alternative strategies to improve recurrence rates after PEH need to be explored in the future.

Introduction

Acetic acid chromoendoscopy (AAC) is frequently used in Barrett esophagus (BE) surveillance endoscopies. AAC is believed to be useful as a ‘red flag’ technique, thereby improving the overall neoplasia detection and the diagnostic yield of targeted biopsies. Accurate targeted neoplasia detection with AAC therefore holds the promise of abandoning random four-quadrant biopsies at 2cm intervals of the BE segment. Although some data exist on the use of AAC in expert centers, the added value in a non-dysplastic surveillance population in routine clinical practice is currently unclear.

Aims & Methods

A prospective stepped wedge cluster randomized trial was conducted in 18 Dutch community hospitals. BE patients undergoing surveillance endoscopies were eligible, while those with known or previously treated dysplasia were excluded. Participating hospitals shifted from usual care (no AAC; control group) to the incorporation of AAC (AAC; intervention group) in randomized order. Endoscopists were trained in the use and assessment of AAC immediately prior to its implementation. In both study groups, targeted biopsies were obtained in the presence of visible lesions before the acquisition of random four-quadrant biopsies. Primary endpoint was the overall neoplasia detection rate, defined as the percentage of patients with low-grade dysplasia (LGD), high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in both targeted and random biopsies, confirmed by an experienced GI pathologist. Secondary endpoint was the neoplasia detection rate of targeted biopsies. Data were analyzed using an as-treated approach, employing mixed effects regression analyses with a random intercept per hospital and correction for calendar time and BE length.

Results

We included 2,267 patients (1570 males; mean age 66) between June 2020 and November 2023. A total of 1,438/2,267 (63%) patients were allocated to usual care and 829/2,267 (37%) to AAC. In patients allocated to AAC, AAC was applied in 679/829 patients (82%). Overall, 163/2,267 patients (7.2%) were diagnosed with neoplasia, which encompassed LGD in 111/2,267 patients (4.9%), HGD in 30/2,267 patients (1.3%), and EAC in 22/2,267 patients (1.0%). The use of AAC did not result in a significantly higher overall neoplasia detection rate (7.4% with AAC [50/679 patients] versus 7.1% without AAC [113/1,588 patients]; OR 0.97; 95% CI 0.65-1.44). Visible lesions were detected in 95/679 (14.0%) patients receiving AAC versus 101/1,588 (6.4%) patients receiving usual care (p<0.001), yet the targeted neoplasia detection rate was not significantly higher (2.1% [14/679 patients] versus 1.8% [29/1,588 patients]; OR 1.05; 95% CI 0.49-2.24). Neoplasia was detected by random four-quadrant biopsies in the majority of patients: 39/50 patients (78%) receiving AAC and 81/113 patients (72%) receiving usual care.

Conclusion

The use of AAC does not improve the overall or targeted neoplasia detection rate in BE patients undergoing endoscopic surveillance in routine clinical practice. Endoscopic surveillance with AAC-guided targeted biopsies cannot replace the random biopsy protocol.

Disclosure

Pentax Medical, C2 Therapeutics

Introduction

Very early onset inflammatory bowel disease (VEO-IBD) is often associated with a severe disease course and unique characteristics including an underlying monogenic defect. In this study, we identified new pathogenic mutations in CGNL1 associated with VEO-IBD and other inflammatory GI disease. CGNL1 (Cingulin Like 1) encodes an epithelial junctional protein whose function was previously unknown in the gastrointestinal tract.

Aims & Methods

Whole exome sequencing (WES) was performed on the affected patient with VEO-IBD and all first-degree relatives with IBD and other inflammatory disease. Intestinal epithelial organoids (IEOs) were generated from the affected patient and were characterized by transepithelial electrical resistance (TEER), FITC-dextran permeability assay on epithelial cell monolayer, immunostaining, RNA sequencing, and transmission electron microscopy (TEM). In addition, we generated a new Cgnl1^-/- mouse model, which was characterized using FITC-dextran permeability assay, TEM, dextran-sodium sulfate (DSS)-induced colitis, and infections by Citrobacter rodentium and Clostridioides difficile. Single-cell datasets were analyzed to determine CGNL1 expression in IBD, primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH).

Results

In the affected patient with VEO-IBD who required early total colectomy and pouch formation with coexistent PSC and celiac disease, WES identified two rare, new, pathogenic variants in the CGNL1 gene. Both pathogenic variants were also present in the patient’s younger sister, who has a similar history including early-onset, fulminant ulcerative colitis requiring total colectomy with ileostomy and PSC-AIH overlap syndrome. Furthermore, multiple relatives of the patient suffer from IBD and other inflammatory conditions including celiac disease, eosinophilic esophagitis, and type-1 diabetes. The RNA and protein levels of CGNL1 were significantly diminished in the patient’s intestinal epithelial cells compared to that of healthy individuals and other IBD patients by RNA-seq, immunoblotting, and immunostaining. The patient’s IEOs from pouch body and pre-pouch ileum formed smaller 3D spheroids with altered cell composition and significantly impaired barrier function compared to those from healthy controls and other IBD patients. Immunofluorescence and TEM demonstrated that CGNL1 is required for the assembly of junctional complexes in human IEOs and an epithelial cell line. Similarly to findings from the patient, impaired junctional complexes in intestinal epithelial cells and elevated intestinal permeability were present in Cgnl1^-/- mice at steady state. Cgnl1^-/- mice showed substantial vulnerability to DSS-induced colitis and bacterial infections that directly compromise the epithelial barrier. In addition, 6-month-old Cgnl1^-/- mice exhibited spontaneous inflammation in the colon and terminal ileum due to disrupted intestinal barrier, which was microbiome-dependent. Furthermore, single-cell analysis revealed diminished expression of CGNL1 in the intestinal and hepatic epithelial cells from patients with IBD or PSC/AIH, respectively.

Conclusion

The pathogenic CGNL1 variants contribute to VEO-IBD by disrupting gut barrier integrity, as demonstrated by patient’s cells and novel murine models. This study expands our understanding of epithelial barrier impairment in the pathogenesis of VEO-IBD, and highlights intestinal epithelium as a therapeutic target in some IBD patients.

Introduction

Functional gastrointestinal disorders (FGIDs), such as irritable bowel syndrome (IBS) and functional dyspepsia, are prevalent conditions within the field of Neurogastroenterology. These disorders have a profound impact on patients’ quality of life and demand a comprehensive biopsychosocial approach to care. Despite evidence in favor of integrated care, treatment remains largely pharmacological. To address this gap, our hospital established a dedicated Functional Neurogastroenterology Unit by incorporating a nurse trained in health coaching and Neuro-Linguistic Programming (NLP) supported by a custom GPT-based artificial intelligence (AI) tool aimed at enhancing patient communication and clinical decision-making.

Results & Findings

A descriptive observational study was conducted on nurse-led consultations between September 2024 and April 2025. The intervention integrated coaching sessions, Neuro-Linguistic Programming (NLP), and the use of a customized GPT-based system to support communication and care planning. Data collected included demographic characteristics, presenting symptoms, and referral patterns. Additionally, each patient was invited to write a personal narrative reflecting on their experience throughout the intervention.

Summary & Discussion

Forty-eight patients were attended during the study period (mean age: 38.6 years; 68.7% female). The most common diagnoses were functional dyspepsia, irritable bowel syndrome, and nonspecific digestive disorders. Frequently reported symptoms included bloating, epigastric pain, early satiety and burning. 20.8% of patients were referred to psychology services and 2.1% to psychiatry. Patient narratives revealed improvements in emotional self-regulation, greater sense of empowerment, and high levels of satisfaction. AI reduced administrative burden, improving focus on direct care, interdisciplinary communication, and adherence to treatment.

Conclusion

Coaching, NLP and AI are effective tools to address FGIDs from nursing, promoting personalized care and improving the patient's emotional well-being.

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