Introduction

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease in which muscle weakness develops insidiously. In advanced stages of the disease dysphagia, weight loss and malnutrition occur in the majority of patients. Thus, the consideration of Percutaneous Endoscopic Gastrostomy (PEG) tube placement is common. However, the optimal timing and setting for the procedure as well desired spirometry results are either are not stated in most guidelines or debated. Previous studies have suggested greater procedural risk for patients whose forced vital capacity (FVC) was less than 50% than predicted

Aims & Methods

The aim of this study was to assess the safety of our tertiary center simplified approach to PEG tube placement in patients with ALS.
The electronical records of patients who underwent percutaneous endoscopic gastrostomy (PEG) placement between 1.1.2020 to 1.1.2023 were retrospectively reviewed. All adult patients diagnosed with ALS who underwent ambulatory PEG tube placement were included. Patients who underwent PEG tube placement during hospitalization due to acute illness were excluded. The common practice of our center regarding PEG placement in patients with ALS is as follows: initial evaluation at the Gastroenterology clinic of patients referred by the neurology clinic, followed by ambulatory PEG placement under sedation by an anesthesiologist. We collected baseline information from the neurology and gastroenterology clinic visits regarding comorbidities and baseline FVC and the functional rating score [ALS-FRS, 0-48 points, lower score indicating a more severe disease). The data concerning the procedure and possible complications were collected from endoscopy reports, emergency department visits and clinic visits after the procedure.

Results

Six hundred and sixty patients had underwent PEG tube placement in our center during study period. Of them, 67 patients had an established diagnosis of ALS (10.2%). One patient was excluded due to PEG placement in the setting of an acute illness during admission, thus 66 patients were included (mean age at PEG placement 63.5±12.7 years and 37.8% were females). Mean ALS-FRS score was 23.6±8.81 and mean FVC was 49.8±19.45% of predicted. More than half (54.7%) of the patients were using non-invasive ventilation support device at home prior to the procedure and 12.1% of patients had underwent endotracheal tube placement prior to PEG tube placement.
The averaged duration of PEG tube placement was 11.96±5.3 minutes. All PEG procedures were completed successfully. Complications were documented during two PEG placements (3%): one patient suffered from aspiration and was hospitalized and later diagnosed with aspiration pneumonia and the second patient suffered from gastric perforation and peritonitis which was diagnosed a few hours after the procedure. During the 30 days following PEG placement, 3 (4.5%) complications were documented: Two patients (3%) suffered from PEG site infections and were treated with antibiotics and one (1.5%) was diagnosed with aspiration pneumonia. No deaths occurred during the procedure or during the 30 days that followed.

Conclusion

The simple straight forward approach to PEG placement in our institution was successful and safe in the vast majority of cases. The complications rate in our cohort is comparable to other studies, even though the patients in our cohort had significantly reduced lung function and functional scores then accepted in the common practice.

References

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2. EFNS Task Force on Diagnosis and Management of Amyotrophic Lateral Sclerosis: Andersen P M, Abrahams S, EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)--revised report of an EFNS task force, Eur J Neurol 2012 Mar;19(3):360-75.
3. Korner S, Hendricks M, Weight loss, dysphagia and supplement intake in patients with amyotrophic lateral sclerosis (ALS): impact on quality of life and therapeutic options, BMC Neurol 13, 84 (2013).
4. Russ K B, Phillips MC, Percutaneous Endoscopic Gastrostomy in Amyotrophic Lateral Sclerosis, Am J Med Sci . 2015 Aug;350(2):95-7.
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6. Thomas K, Schrager J, Percutaneous endoscopic gastrostomy tube placement in amyotrophic lateral sclerosis: a case series with a multidisciplinary, team-based approach, Ann Gastroenterol 2020 Sep-Oct;33(5):480-484

Introduction

Colorectal cancer associated to chronic colitis (CAC) has a different pathogenesis compared to sporadic or familial colorectal cancer (CRC) and represents the major complication of inflammatory bowel disease (IBD). It is now well-established that IL-33 and its receptor, ST2, are important factors in the pathogenesis of IBD. Emerging evidence also suggests its critical role in epithelial proliferation and the potential contribution to inflammation-driven tumorigenesis that can lead to CRC.

Aims & Methods

The aim of our study was to characterize the precise contribution of IL-33/ST2 axis in the azoxymethane (AOM)/dextran sodium sulfate (DSS) model of colitis-associated CRC. C57/BL6 wild-type (WT), Il33^-/-, T1/St2^-/- and Nt5e^-/- mice were given a single dose of AOM (10 mg/kg) followed by two cycles of 3% DSS for 7d in drinking water. Vehicle-treated WT mice served as controls and were sacrificed at the same time points. Another group of WT followed the same protocol and received CD73 inhibitor i.p. treatment or vehicle. Disease Activity Index (DAI), as well as endoscopic, stereomicroscopic and histological evaluations of colons were performed. IHC, immunofluorescence (IF), qPCR, and ELISA were done on full-thickness colons of WT for IL-33 and ST2 localization and identification, as well as mRNA and protein expression, respectively. RNA-Seq was performed on whole tissues from AOM/DSS treated WT, Il33^-/- and T1/St2^-/-. qPCR analysis was done on isolated polyps from WT, Il33^-/- and T1/St2^-/- for Nt5e (CD73) and adenosine pathway targets.

Results

Il33, Ilrl1(ST2L), and Ilrl1(sST2) mRNA transcripts, as well as IL-33 and total ST2 proteins were dramatically elevated in AOM/DSS-treated WT mice vs. controls. IHC and IF of treated WT mice revealed localization of IL-33 to the colonic epithelium and to cells within the polyp LP morphologically consistent with stromal and mast cells. Little to no staining for IL-33 was present in controls. Using IF, IL-33 co-localized with sub-epithelial myofibroblast markers Actin and Vimentin, or with mast cell markers Tryptase and MCPT1. AOM/DSS treatment in Il33^-/- and T1/St2^-/- mice resulted in a significant decreased polyp number and size vs. WT, with colonoscopy revealing the development of protruding lesions with abnormal vascular patterns, suggesting tumorous lesions in WT mice, while all deficient mice showed their absence with a more impressive mucosal inflammation, likely due to reduced epithelial proliferation and repair caused by the deficiency of IL-33 signaling. RNA-Seq identified a significant reduction of Nt5e and adenosine pathway targets in Il33^-/- and T1/St2^-/- vs. WT. qPCR on isolated polyps confirmed this observation. AOM/DSS-treated Nt5e^-/- showed a significant decreased polyp number and size vs. controls. Therapeutic inhibition of CD73 produced similar results.

Conclusion

Our results suggest that the IL-33/ST2 axis promotes tumorigenesis in colitis-associated CRC through the activation of CD73. Further studies are underway to determine mechanisms of action that support these findings.

Introduction

Capsule endoscopy is the first-line examination for digestive bleeding with likely origin in the small bowel, in hemodynamically stable patients. In the 2022 update, ESGE guidelines recommend that, in the context of overt bleeding, capsule enteroscopy should be performed as soon as possible, ideally within the first 48 hours. In the previous guidelines, published in 2015, the recommended window was 14 days.

Aims & Methods

This study aimed to evaluate the improvement in yield offered by the new recommendations regarding the timing of urgent capsule enteroscopy. Patients with suspected overt middle gastrointestinal bleeding between January 2005 and November 2022 were retrospectively analyzed. Diagnostic and therapeutic yield, rebleeding rate, and mortality were compared when capsule enteroscopy was performed within the first 48 hours, within the first 14 days, or between the 3rd and 14th day after admission.

Results

A total of 138 patients were included (58.7% men, median age 66 years), 87 of whom (63.0%) underwent capsule enteroscopy within the first 48 hours after hospital admission. The median follow-up was 55 months (5-180). The diagnostic yield (presence of blood or lesions with bleeding potential) was slightly higher when capsule enteroscopy was performed within the first 48 hours (81.6% versus 76.5%, p=0.349). On the other hand, capsule enteroscopy within the first 48 hours was significantly associated with higher therapeutic yield (endoscopic, radiologic, or surgical treatment) - 54.0% versus 39.2%, p=0.02. The rebleeding rate was significantly lower in patients undergoing enteroscopy within 48 hours after admission (19.5% versus 29.4%, p=0.04). On the other hand, overall mortality at 36 months did not differ between strategies (21.8% and 25.5%, p=0.401).

Conclusion

Performing capsule endoscopy within the first 48 hours, as recommended by recently published guidelines, is associated with favourable short- and long-term clinical outcomes.

Introduction

Percutaneous endoscopic gastrostomy (PEG) is recommended for long-term enteral nutrition in dysphagic patients with a vast heterogeneous group of underlying conditions. Decision-making for gastrostomy placement requires careful consideration on a case-by-case basis, with the underlying condition, clinical status and prognosis taken into account. Although estimating prognosis is a critical factor in the decision-making of PEG tube placement, it remains challenging and heavily reliant on clinical judgement.

Aims & Methods

Retrospective study of adult patients who underwent PEG in a tertiary hospital from 2001 to 2023. This study aims to characterize conditions motivating PEG, assess nutritional status on the gastrostomy day, evaluate survival and search for survival predictors. Data collected included demographics, underlying disorders, nutritional status (anthropometry/laboratory evaluation) on the day of PEG and survival recorded until death or December 2023. Multivariable analysis was performed with Cox regression to search for survival predictors.

Results

A total of 1415 patients were included (61.8% males, mean age 66.9 years); 66.4% presented a neurological disorder (35.3% with a potentially regressive course and 31.2% with a progressive course) and 31.3% head and neck or esophageal cancers (HNC/EC). The most frequent underlying conditions were post-stroke dysphagia (25.5%), dementia (11%) and amyotrophic lateral sclerosis (10.8%). The mean BMI was 20.9 kg/m2, with 49.8% underweight patients. Albumin, transferrin and total cholesterol were low at 43.2%, 62.2% and 50%, respectively. Median overall survival was 11.1 months, with a 1-, 3- and 5-year survival rates of 48.2%, 27.8% and 19.6%, respectively. 14.1% of deaths occurred within 4 weeks. These short survivors were significantly older and had lower mean albumin, transferrin and total cholesterol levels. Although BMI was also lower, this difference did not reach statistical significance. Potentially regressive neurological conditions presented higher survival than progressive ones (16.6 vs. 13.3 months, p = 0.004). HNC/EC patients presented a significantly lower survival (6.6 months) when compared to both of these groups (p < 0.001). Besides underlying condition, predictors of increased survival on the multivariable analysis included female gender (HR 0.396), younger age (HR 0.980), higher albumin (HR 0.687) and higher BMI (HR 0.963). The protective effect of BMI and albumin was more pronounced in males than in females.

Conclusion

Neurological disorders were the most frequent underlying conditions. Nearly half of the patients displayed malnutrition before PEG feeding. Although PEG-fed patients displayed a considerable median survival time, some died early without benefit from PEG. Patients with potentially regressive neurological conditions presented better outcomes. Female gender, younger age, higher albumin and higher BMI were associated with longer survival. The findings emphasize the complex interplay of clinical, demographic and nutritional factors influencing survival after PEG tube placement. By integrating these predictors of survival into clinical practice, patient selection can be tailored in order to optimize outcomes.