Introduction

The need for multidisciplinary and expert 24/7 emergency care for acute mesenteric ischemia (AMI) has led to the implementation of the first Intestinal Stroke Center (ISC) in France in 2016. This study aimed to report our results at 7 years.

Aims & Methods

A prospective cohort study was conducted in our ISC unit and included all patients admitted for acute and chronic mesenteric ischemia (CMI) or dissections of coeliomesenteric arteries without ischemia. All patients were treated according to our multimodal and multidisciplinary protocol previously published (Corcos et al. Clin Gastroenterol Hepatol 2013). Patients are treated 24/7 by an on-call gastroenterologist coordinating management and care pathways between interventional radiologists, vascular and digestive surgeons, and intensivists. Patients were then followed with a clinical visit and CT angiography at 1, 3, 6, 12, and 24 months.

Results

Between January 1, 2016 and October 1, 2022, we received 3,910 calls concerning 2,525 patients, 84% from the Paris region and 14.5% from other regions of France. This represents an average of 361 patients/year, with an annual increase in calls of 35%, going from 155 calls the first year to 684 calls for the last year. We hospitalized 719 patients (103 patients/year on average), with a median age of 65 years (IQR 54-74), of which 42% were women, and including 493 AMI (69%), 106 CMI (15%) and 116 dissections of coeliomesenteric arteries (16%). Among patients hospitalized for AMI (n=493), 395 (80%) were secondary to arterial occlusion and 87 (20%) to porto-mesenteric venous thrombosis. In the AMI group, the revascularization rate was 72% for arterial AMI (0% for venous forms), and the resection rate was 57%. The 1-year survival was 75% for arterial AMI and 97% for venous forms. In the subgroup of AMI referred to our center within the first seven days (n=373), the bowel resection rate was 39%, and the 1-year survival rate was 79%. In the CMI group (n=106), the revascularization rate was 78%, the bowel resection rate was 1%, and the 1-year survival rate was 92%. In the dissections of coeliomesenteric arteries without ischemia (n=116), the treatment was mainly medical, with a revascularization rate of 3%, with no intestinal resection or death occurring at 1 year.

Conclusion

This large prospective study is the first to report on the activity and results of a specialized ISC for mesenteric ischemia and intestinal vascular diseases. Our results show that creating an ISC with standardized management focused on intestinal viability opened a recruitment channel for these severe patients with survival > 70% and resection rates < 50%, particularly in patients admitted at an early stage. These results encourage the creation of other regional ISCs in France and other countries as a new standard of care in AMI.

Disclosure

MSD Avenir grant

Introduction

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) induce weight loss, and have been associated with an overall decreased risk of esophageal cancer. Obesity is strongly associated with esophageal adenocarcinoma and substantial weight loss may decrease the risk of this malignancy, whereas weight loss does not decrease the risk of esophageal squamous cell carcinoma. We examined the hypotheses that GLP-1RA treatment decreases the risk of esophageal adenocarcinoma.

Aims & Methods

This population-based case-control study included all cases of esophageal adenocarcinoma and esophageal squamous cell carcinoma in adults who had dispensed medication for type 2 diabetes in Denmark (2007-2020), Finland (2011-2018), Iceland (2009-2019), Norway (2007-2019), or Sweden (2007-2020). For each case participant, >10 control participants who had dispensed medication for type 2 diabetes were randomly sampled from the general populations. Data came from well-validated nationwide health-data registries with prospectively collected data. Multivariable logistic regression provided odds ratios (OR) for esophageal adenocarcinoma and esophageal squamous cell carcinoma with 95% confidence intervals (CI), adjusted for sex, age, calendar year, country, comorbidity, obesity, alcohol overconsumption, and tobacco smoking.

Results

This study included 2,909 case participants with esophageal adenocarcinoma, 670 case participants with esophageal squamous cell carcinoma, and 55,408 control participants. The risk of esophageal adenocarcinoma was not decreased in GLP-1RA users compared with non-users (adjusted OR 1.3, 95% CI 1.1-1.5). However, the risk of esophageal squamous cell carcinoma was decreased (adjusted OR 0.5, 95% CI 0.3-0.8).

Conclusion

Standard GLP-1RA treatment in patients with type 2 diabetes might not decrease the risk of esophageal adenocarcinoma. Confounding by indication may have been the most important, or even the sole, contributor to the decreased risk of esophageal squamous cell carcinoma observed, although anticarcinogenic mechanisms of GLP-1RAs other than weight loss cannot be ruled out.

Introduction

Intestinal ischemia-reperfusion injury (IRI) is a life-threatening condition caused by an abrupt obstruction of mesenteric blood flow. Reestablishing blood flow (reperfusion) is necessary to save intestinal tissue but unintentionally exacerbates damage induced by ischemia. Mitochondria are sensitive to IRI; if damaged, they release cytotoxic molecules that can aggravate injury. Therefore, removal of damaged mitochondria is essential for cellular survival. The selective clearance of mitochondria via autophagy, mitophagy, has been reported to protect against IRI in other organs, but its role in the intestine remains unknown.

Aims & Methods

The main objective of this study was to assess mitochondrial damage and evaluate signs of mitophagy in response to hypoxia-reoxygenation in a human small intestinal organoid (SIO) model and the differences therein between crypt-like (CL) and villus-like (VL) organoids. Both SIOs phenotypes were exposed to hypoxia-reoxygenation, and mitochondrial damage was assessed by live-cell imaging of mitochondrial membrane potential using fluorescent dye tetramethylrhodamine methyl ester (TMRM). In addition, ultrastructural changes in mitochondria were evaluated by transmission electron microscopy (TEM). Finally, mitochondrial content, autophagy, and mitophagy markers were assessed using quantitative PCR (qPCR) and Western blot.

Results

A drastic decrease in TMRM fluorescence, indicating impaired mitochondrial activity, was mainly observed in VL organoids and not in CL organoids. Mitochondrial ultrastructural changes were observed in both phenotypes, including mitochondrial swelling and disrupted cristae following hypoxia, whereas after 480 minutes reoxygenation, mitochondria exhibited a tubular or small round shape. Mitochondrial content markers were decreased in both organoid phenotypes following hypoxia-reoxygenation. Most importantly, only CL organoids showed a significant increase in autophagy and mitophagy markers.

Conclusion

Mitochondria of VL organoids are more severely damaged by hypoxia-reoxygenation, whereas CL organoids might be protected by inducing mitophagy. The occurrence of mitophagy is currently further validated with live-cell imaging.

Introduction

High-definition anorectal manometry (HD-ARM), balloon expulsion test (BET) and magnetic resonance defecography (MR-defecography) are important tools in studying constipation.

Aims & Methods

Evaluate the prevalence of functional defecation disorders and structural anorectal alterations in patients with constipation and compare the findings of HD-ARM and BET with MR-defecography.
Retrospective cohort study including patients with functional constipation (FC) or irritable bowel syndrome with constipation (IBS-C) submitted to HD-ARM, BET and MR-defecography. Patients were divided into three groups: 1) normal anorectal evacuation pattern in HD-ARM and BET; 2) abnormal anorectal evacuation pattern and BET; 3) normal anorectal evacuation pattern and abnormal BET, or abnormal anorectal evacuation pattern and normal BET.

Results

A total of 64 patients were included, 49 with FC (76.6%) and 15 with IBS-C (23.4%). There were 20 patients in group 1 (31.3%), 11 in group 2 (17.2%) and 33 in group 3 (51.5%). In MR-defecography, 47 patients had relevant structural anorectal alterations (73.4%) and 15 had an abnormal contraction of the puborectalis during the defecatory maneuver (23.4%).
Nineteen patients were diagnosed with dyssynergic defecation (29.7%). These patients had significantly higher residual anal pressure and lower percentage of anal relaxation during defecation (109.6±43.2 vs 85.8±29.7 mmHg, p=0.038 and 9% vs 24%, p=0.018, respectively), as well as a lower differential of rectoanal pressure (-32.2±31.4 vs 3.0±29.6 mmHg, p<0.001).
Patients with structural anorectal alterations had a significantly higher body mass index (BMI) (27.4±4.5 vs 23.5±3.3, p=0.002), and all obese patients had structural alterations.
Comparing the findings of HD-ARM and BET with MR-defecography: in group 1, 15 patients had structural alterations (75.0%); in group 2, 8 patients had structural alterations (72.7%); in group 3, 22 patients only had structural alterations (66.7%), 6 only had dyssynergic defecation (18.2%), 2 patients had both (6.0%) and 3 did not have any findings (9.1%). In 24.2% of patients with inconclusive findings in HD-ARM and BET, MR-defecography allowed the diagnosis of dyssynergic defecation.

Conclusion

Patients with structural anorectal alterations had a significantly higher BMI. Almost three quarters of patients with FC and IBS-C had relevant structural anorectal alterations and one third had dyssynergic defecation. Therefore, it is important to combine MR-defecography with HD-ARM and BET in the study of constipation.