Clinical Case Summary

Case: W present a case of a 43-year-old man with hepatic cirrhosis complicated by hypertensive gastrointestinal bleeding, in a program to eradicate esophageal varices. One week after an elective endoscopic variceal ligation (EVL), he presented with fever, anorexia, pain in the dorsolumbar region, headaches, and psychomotor retardation. Subsequently, there was the appearance of focal motor seizures. The analyses showed C-reactive protein of 113 mg/L, without leukocytosis. Peripheral blood cultures were negative. A head computed tomography (CT) showed mild left parietal and occipital cortical hypodensities. Analysis of the cerebrospinal fluid was compatible with central nervous system (CNS) infection. Cerebral magnetic resonance revealed multiple supra and infratentorial rounded lesions, compatible with abscesses and ventriculitis. He started antibiotics with a meningeal dose. Hospitalization was complicated by SARS-COV 2 infection, so a chest CT was performed after 1 month of hospitalization, and was identified a mediastinal abscess with 5 cm with fistulization from the esophagus, compatible with iatrogenic esophageal perforation after EVL. Other possible causes of brain abscesses were excluded. He completed several weeks of antibiotic and parenteral nutrition, with normalization of the neurological status and resolution of brain lesions. About 1 month after targeted antibiotic treatment, he performed an endoscopy, revealing a deformed area in the distal esophagus but no evidence of an orifice or suppuration. Conclusion: Neurological manifestations in patients with liver cirrhosis are usually due to hepatic encephalopathy (HE). However, CNS infection, especially in patients who underwent recent procedures, such as EBL, should be considered in the differential diagnosis, given that early treatment influences the prognosis. Clinically, CNS infection can be very variable, however, it is important to be aware of atypical signs of HE, such as focal neurological deficits.

References

Krige JE, Bornman PC, Shaw JM, Apostolou C. Complications of endoscopic variceal therapy. S Afr J Surg. 2005 Nov;43(4):177-88, 190-4.

Disclosure

Nothing to disclosure

Introduction

The introduction of lumen-apposing metal stents (LAMSs) has revolutionized the field of therapeutic endoscopic ultrasound (EUS). In the last decade, its utilization for off-label indications has markedly increased, particularly among patients with surgically altered anatomy to establish access in the excluded segment of the gastrointestinal tract. Indications for anastomosis creation include EUS-directed transgastric endoscopic retrograde cholangiopancreatography (EDGE), EUS-directed transgastric intervention (EDGI), or endoscopic reversal of Roux-en-Y gastric bypass (RYGB) for specific indications (see below).

Aims & Methods

This study aims to evaluate the effectiveness and safety of LAMS in patients with surgically altered anatomy for EDGE, EDGI, and reversal of RYGB. We collected data on all LAMS procedures conducted in patients with surgically altered anatomy, between October 2019 and February 2024 at the University Hospital of Ghent.
We used our prospective LAMS database and retrieved missing data from retrospective analysis of the medical patient records. The main outcome data of interest were technical success, clinical success, and adverse events. Technical success was defined as a successful placement of LAMS in the desired position. Clinical success was defined as either successful endoscopic access to the intended excluded gastrointestinal segment or achievement of the intended therapeutic goal when RYGB reversal was necessary. Adverse events were classified according to the AGREE criteria.

Results

A total of 73 LAMS procedures were performed: 70 cases of EUS-guided gastro-gastrostomy in patients with RYGB and 3 cases of EUS-guided gastro-enterostomy in patients with hepaticojejunostomy. Indications for LAMS procedures included 55 (75.3%) cases of EDGE, 13 (17.8%) cases of EDGI (such as gastroduodenoscopy and EUS), and 5 (6.8%) cases of RYGB reversal. Reversal of RYGB was required for one cachectic patient due to metastatic cholangiocarcinoma, three patients with hyperinsulinemic hypoglycemia, and one patient with therapy-resistant small intestinal bacterial overgrowth (SIBO).
The overall technical and clinical success rates were very high at 97.3% and 95.9%, respectively. Adverse events were observed in 11 out of 73 (15.1%) cases, including 7 (9.6%) minor events (AGREE score < 3) and 4 (5.5%) major events (AGREE score ≥ 3). Major events included stent migration (N=1), persistent fistula (N=2), and respiratory desaturation (N=1). All events could be successfully managed, and there were no procedure-related deaths. In 69.9% of cases, our method involved a dual-step approach, strategically implemented to await fistula maturation and reduce the risk of perforation. The median LAMS dwell time was 38 days (range 7, 431). LAMS was removed in 72.6% of the cases. Loss of LAMS patency occurred in 1 out of 73 (1.4%) cases and was endoscopically managed.

Conclusion

In conclusion, our study demonstrates that EUS-GG and EUS-GE offer an effective and safe approach to create anastomoses between gastrointestinal (GI) segments when performed by experts. With high technical (97.3%) and clinical (95.9%) success rates, LAMS proves beneficial for accessing excluded GI segments and reversing RYGB. Adverse events (15.1%) were mostly minor and manageable, with no procedure-related mortality. The extended patency duration and low re-intervention rate highlight LAMS as a minimally invasive and durable option in therapeutic endoscopic ultrasound procedures. Further prospective studies are required.

Introduction

Etiology of acute pancreatitis can be established in the majority of patients. However, in 25 % of cases it remains elusive. Biliary microlithiasis/sludge is detected in up to 75% of patients with idiopathic acute pancreatitis (IAP). As recurrent biliary pancreatitis can be prevented, the underlying etiology of IAP should be established. The aim of this multicentre retrospective study was to develop a machine learning-aided non-invasive prediction tool to guide clinicians in the selection of idiopathic acute pancreatitis patients to be referred to endosonography to establish etiology and allow treatment.

Aims & Methods

We retrospectively used routinely recorded clinical and laboratory parameters of 218 consecutive patients with confirmed acute pancreatitis admitted to our tertiary care hospital between 2015 and 2020. Patients who did not receive endosonography as part of the diagnostic work-up and whose pancreatitis episode could be adequately explained by other causes than biliary sludge and microlithiasis were excluded. We trained supervised machine learning classifiers using H2O.ai automatically selecting the best suitable predictor model to predict microlithiasis/sludge. The predictor model was validated in two independent retrospective cohorts from two tertiary care centers (TU Munich & University Medical Center Göttingen).

Results

28 categorized patients’ variables recorded at admission were identified to compute the predictor model with an accuracy of 0.84 [95% CI 0.791, 0.9185], positive predictive value of 0.84 and negative predictive value 0.80 in the identification cohort (218 patients). In the validation cohort, the robustness of the prediction model was confirmed with an accuracy of 0.76 [95% CI 0.673, 0.8347], positive predictive value of 0.76 and negative predictive value of 0.78 (117 patients).

Conclusion

We present a robust and validated machine learning-based predictor model consisting of routinely recorded lab work at admission that can predict biliary sludge and microlithiasis as cause of acute pancreatitis and select patients for EUS.

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

Endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) with esophageal varices (EVs) is one of the most challenging endoscopic procedures due to the high risk of bleeding and fibrosis caused by prior treatment of varices. However, due to the small number of such cases, the clinical outcomes of ESD for ESCC with EVs have been reported in only a limited number of cases at single centers^​1-3.

Aims & Methods

We conducted a multicenter, retrospective, cohort study to clarify the safety and efficacy of ESD for ESCC with EVs.Eleven institutions in the Tohoku region of Japan participated in this multicenter, collaborative, retrospective study. We performed endoscopic resection for 3619 patients with esophageal carcinoma at the participating institutions during the period from January 2010 to April 2022. Among those, 30 patients who underwent ESD for ESCC with EVs were recruited for the present study.
Rates of en bloc resection and R0 resection, procedure time and adverse events were evaluated as indicators of the feasibility and safety of ESD. Additional treatment, recurrence and metastasis of the lesions were evaluated as indicators of the long-term efficacy of ESD.

Results

Portal hypertension was caused by cirrhosis, of which alcohol was the most common cause. En bloc resection was achieved in 93.3% and R0 resection in 80.0% of the patients. The median procedure time was 92 minutes. Adverse events included a case of uncontrolled intraoperative bleeding leading to discontinuation of ESD and a case of esophageal stricture due to extensive resection. During the follow-up period of a median for 42 months, a patient with local recurrence and another patient with liver metastasis were observed. One patient died of liver failure after receiving chemoradiotherapy as an additional treatment after ESD. No patient died of ESCC.

Conclusion

This multicenter, retrospective cohort study demonstrated the safety and efficacy of ESD for ESCC with EVs. Further studies are needed to establish appropriate treatment methods for EVs before ESD and additional treatments for patients with insufficient ESD.

References

1. Sawaguchi M, Jin M, Matsuhashi T, et al. The feasibility of endoscopic submucosal dissection for superficial esophageal cancer in patients with cirrhosis (with video). Gastrointest Endosc 2014;79:681-5.
2. Choi YK, Noh JH, Kim DH, et al. Outcomes of endoscopic submucosal dissection for superficial esophageal neoplasms in patients with liver cirrhosis. Clin Endosc 2022;55:381-9.
3. Zhang S, Liu YD, Chai NL, et al. Endoscopic submucosal dissection for early cancers or precancerous lesions of the upper gastrointestinal tract in cirrhotic patients with esophagogastric varices: Ten-year experience from a large tertiary center in China. Gastrointest Endosc 2023 Online ahead of print.

Disclosure

The authors declare that they have no conflicts of interest.