Introduction

The incidence of acute pancreatitis (AP) has been steadily increasing worldwide and the burden of disease can become greater if severe late phase complications occur. However, there is currently no prediction tool available in early phase for this specific clinical situation. We aimed to establish a prediction model with early phase parameters to estimate the need for intervention and late phase mortality.

Aims & Methods

We selected patients from a retrospectively collected AP cohort of five university hospitals that contained data of patient with AP from 2010 to 2022. The endpoint was defined as late phase pancreatitis-related mortality or endoscopic, percutaneous, vascular, or surgical intervention for complications within six months after admission. We randomly split the cohort into development and validation sets with a ratio of 7:3. The model was developed by logistic regression, and the diagnostic performance was analyzed using area under the curve (AUC).

Results

We identified 2,497 patients with AP (1,748 in the training set; 749 in the validation set) with a total endpoint rate of 3.1%. Two models were established using four variables at admission (Systemic Inflammatory Response Syndrome, organ failure, calcium <8.5 mg/dL, albumin <3.45 g/dL) and four variables after 48 hours of admission (Fever, organ failure, CRP ≥200 mg/L, CT Severity Index (CTSI) ≥5). Model #1 consists of variables at admission only, and Model #2 consists of all eight admission and 48hr variables. Model #2 had an AUC of 0.835 and 0.790 in the development and validation set, respectively. Model #2 showed significantly higher AUC to predict late-phase severe complications compared to Model #1 and other systems such as Ranson`s criteria, BISAP score, and CTSI. Using two established models sequentially, patients can be classified into four groups with different rates of late phase severe complications (15.2% vs. 9.5% vs. 2.8% vs. 0.9%; P<.001).

Conclusion

We developed a set of early prediction models to predict the likelihood of eventual mortality or intervention in the late phase of AP within 6 months. These models can stratify the long-term prognosis of AP and help with appropriate allocation of medical resources for intensive care and interventional procedures.

Introduction

Although endoscopic submucosal dissection (ESD) is established as first-choice treatment for early esophageal squamous cell carcinoma (ESCC) worldwide, most data on outcomes are derived from Asian studies. Therefore, we aimed to evaluate the short- and long-term outcomes of ESD for patients with early ESCC in a Western cohort.

Aims & Methods

In this retrospective cohort study, patients with early ESCC amendable for ESD were included in four tertiary referral hospitals in the Netherlands between 2012 and 2017. All procedures were performed by experienced endoscopists who were specifically trained in ESD. The decision for and choice of additional treatment following ESD was made on a per-patient basis. For this study, dedicated research fellows collected all relevant data by reviewing the electronic patients files. Data concerning long-term outcomes were checked with general practitioners or referral hospitals, when applicable. Outcomes included technical success, R0 resection (i.e. tumor-free lateral and vertical margins), curative resection (i.e. en-bloc radical resection with histology no more advanced than T1sm1, good differentiation and absence of lymphovascular invasion) and recurrence rates, as well as ESCC-specific and overall survival.

Results

We included 68 patients (34 males; mean age 69) with a median tumor size of 3cm (range 1-12) and circumferential extent of 50% (range 10-100), in whom ESD was technically successful in 66/68 patients (97%). While en-bloc resection was achieved in 64/66 technically successful ESDs (97%), R0 resection was accomplished in 54/66 patients (82%). Overall, a curative resection was achieved in only 34/66 patients (52%). Among the patients with a non-curative resection, 16/32 (50%) underwent additional treatment receiving either argon plasma coagulation for tumor-positive resection margins (n=1), selective lymph node dissection (n=1), definite chemoradiation therapy (n=4) or esophagectomy ± neoadjuvant chemoradiation therapy (n=10). Endoscopic surveillance was preferred in the other half of patients with a non-curative resection (16/32; 50%) based on significant comorbidities or patient choice. During a median follow-up of 66 months (p25-p75 43-88), 12/66 patients (18%) developed a local recurrence which could be treated endoscopically in most cases (10/12; 83%). Locoregional lymph node metastasis and distant metastasis were observed in 6 (6/66; 9%) and 3 (3/66; 5%) patients, respectively. A total of 30 patients (30/66; 45%) died during follow-up, of which the minority (7/30; 23%) was ESCC-related deaths. The 5-year overall and ESCC-specific survival probability were 64% (95% CI 53-76%) and 88% (95% CI 79-97%), respectively. More importantly, overall survival did not significantly differ between patients with and without curative resections (p = 0.69). In addition, no significant difference was seen for ESCC-specific survival between patients with or without additional treatment after a non-curative resection (p = 0.07).

Conclusion

In this Western cohort with long-term follow-up, the efficacy and safety of ESD for early ESCC was confirmed although the rate of non-curative resections was substantial. Irrespective of non-curative or curative resection, the long-term prognosis of these patients was limited mainly due to competing mortality. Considering additional treatment after a non-curative resection did not influence survival, the potential benefit of adjuvant therapy should be carefully balanced against the risk of dying from another cause than esophageal cancer on an individual basis.

Disclosure

C.N. Frederiks has received speaker's fee from Pentax Medical.
R.E. Pouw is a consultant for MicroTech, and has received speaker’s fee from Medtronic.
J.J.G.H.M. Bergman is a consultant for Medtronic, Cook Medical, and Boston Scientific, and has received research funding from Pentax Medical, C2 Therapeutics, Medtronic, Aqua Medical, Olympus Endoscopy, and Fuji-film.
B.L.A.M. Weusten has received research funding from Pentax Medical, C2 Therapeutics, and Aqua Medical. The remaining authors declare to have no disclosures relevant to this manuscript.

Introduction

Gastric dysplasia in the absence of an endoscopically defined lesion is rare, usually either a false positive diagnosis or a previously unidentified precancerous lesion during esophagogastroduodenoscopy (EGD).

Aims & Methods

The aim of this study was to evaluate factors associated with the presence of an endoscopically visible lesion during follow-up in patients with histologic diagnosis of gastric dysplasia in random biopsies.
Retrospective cohort study including patients referred to our institution for gastric dysplasia detected in random biopsies during EGD (Index EGD). In our institution, endoscopic evaluation was performed with a high-definition endoscope using narrow band imaging (HD EGD-0). If no lesion was detected, endoscopic surveillance (HD EGD-FU) was conducted, depending on the originally detected dysplasia: within 6 months for high grade dysplasia (HGD), 12 months for low grade dysplasia (LGD) or indefinite for dysplasia (IFD).

Results

Regarding Index EDG, from a total sample of 96 patients, most patients had LGD (87.4%), 10 patients had IFD (10.4%) and 2 HGD (2.1%), while the location of the dysplasia was the corpus in 8 patients (8.3%), the antrum in 65 (67.7%) and both in 23 (24%).
During the HD EGD-0, 5 (5.2%) presented with an endoscopically visible lesion, while 10 lesions (10.4%) were identified during HD EGD-FU; 80% of the identified lesions were in the antrum.
Patients with Helicobacter pylori infection identified at Index EDG were 8 times more likely to have an endoscopically visible lesion on HD EGD-FU (OR 8.000, 95%CI 1.588-40.299, p=0.012). Additionally, patients with a regular alcohol consumption (≥25 grams daily) were 4 times more likely to have an endoscopically visible lesion on HD EGD-FU (OR 4.063, 95%CI 1.048-15.748, p=0.047). In fact, both Helicobacter pylori infection identified at Index EGD, and regular alcohol consumption were independent predictors of the presence of gastric lesion on HD EGD-FU in binary logistic regression (OR 9.284, 95%CI 1.724-49.979, p=0.009 and OR 5.025, 95%CI 1.136-22.222, p=0.033, respectively).
The grade of dysplasia and location of the biopsies with dysplasia were neither associated with the presence of lesions during follow-up, nor family history of gastric cancer.

Conclusion

The presence of an endoscopically visible lesion occurred in 15.6% of patients with the previous histologic diagnosis of gastric dysplasia in random biopsies and most lesions were identified in the HD EGD-FU. Both Helicobacter pylori infection identified at Index EGD, and regular alcohol consumption were significant predictors of the presence of gastric lesion on HD EGD-FU.

Introduction

Irritable bowel syndrome (IBS) is a complex multifactorial disorder characterized by recurrent abdominal pain associated with defecation or a change in bowel habits. Patients with IBS often complain of extra-intestinal symptoms resulting in impaired related quality of life. Growing evidence support the hypothesis that intestinal barrier dysfunction has a central role in the pathophysiology of IBS being the interface between the gut lumen and the deeper intestinal layers as well as the brain.

Aims & Methods

The aims of this study were: to characterize the epithelial and vascular barriers; to correlate molecular, morphological and functional aspects of epithelial and vascular barriers with IBS symptoms. 66 healthy subjects (AC) and 223 patients with IBS (112 IBS-D, 58 IBS-C and 53 IBS-M) were enrolled in the study. Rome IV criteria, Bowel disease questionnaire, Short Form 36, Hospital Anxiety Depression Scale were used to phenotype patients. Sugar test was used to evaluate in vivo permeability. The vascular barrier was characterized by using immunohistochemistry, western blot and electron microscopy. Vascular permeability was evaluated by assessing two markers: plasmalemma vesicle–associated protein-1 (PV1) and vascular endothelial cadherin (VEC). A translational model based on Caco-2 cells or HUVEC was used to evaluate permeability changes induced by mediators spontaneously released by mucosal biopsies and to highlight the underlying molecular mechanisms. Correlation analyses have been performed among experimental and clinical data.

Results

Compared to AC, lactulose (P<0.05), sucralose (P<0.01), sucrose (P<0.01) excretion and the L/M ratio (P<0.01) were significantly increased in IBS patients. Soluble mediators released by mucosal biopsies of IBS patients increased Caco-2 permeability compared to AC mediators (P<0.05) via a down-regulation of tight junction gene expression. Blood vessels were significantly increased by 1.5 fold in the colonic mucosa of IBS patients compared to AC (P<0.01). PV1 expression was increased (P<0.01) while VEC expression was decreased in the colonic mucosa of IBS group compared to AC (P<0.05). IBS mucosal mediators increased HUVEC permeability compared to AC mediators. The HUVEC changes associated with IBS samples were mediated by a protease-activated receptor (PAR)2 dependent mechanism resulting in VEC down-regulation. Significant correlations emerged among permeability changes and intestinal, extra-intestinal symptoms and health-related quality of life reported by IBS patients.

Conclusion

Epithelial and vascular barriers are compromised in IBS and are likely involved in symptom development.

Disclosure

Nothing to disclose